Development of a new method for the analysis of sphinganine and sphingosine in urine and tissues

The fumonisins are inhibitors of de novo sphingolipid biosynthesis in vitro and in vivo and thus possibly interfere with the regulation of cell growth, differentiation, and neoplastic transformation. In addition, the ratio of free sphinganine (Sa) to free sphingosine (So) has been proposed as a marker of exposure for animals or humans consuming feed or food contaminated by these toxins. A method to analyze these sphingolipid bases has been proposed [Merrill et al., 1988: Anal Biochem 171:373-381; Riley et al., 1994a: JAOAC 77:533-540] but involves numerous steps and consequently is not ideally suited to the analysis of large numbers of samples, as is often required in epidemiological studies. A new method was therefore developed for the analysis of the Sa/So ratio in tissues as well as human and rat urine. Briefly, the method involves isolation of exfoliated cells from as little as 0.5 ml of rat urine or 2 ml of human urine followed by a rapid and efficient extraction of sphingolipid bases in ethyl acetate, an optimized derivatization step with o-phthaldialdehyde and a high-pressure liquid chromatography separation on a 250 mm x 4.6 mm. 5 microns Kromasil C18 column, with a 4-step phosphate buffer/methanol gradient. Fluorescence was monitored at 340 nm excitation, 455 nm emission, and retention times for So, Sa, and C-20 Sa were about 11, 14, and 22 min, respectively. The method was adapted to tissue analysis by partially digesting approximately 30 mg tissue with trypsin to permit isolation of a cell pellet before extraction of the sphingolipids as described above. The method was applied to the analysis of So and Sa in urines and tissues of fumonisin B1 (FB1) treated and untreated male BDIV rats. The Sa/So ratio in urine of untreated rats varied from 0.1 to 0.7, and for treated rats (between 1-5 mg FB1/kg body weight daily by gavage), the ratio was between 1.2-10. In kidney, the ratio was 0.1 in control rats and varied from 4 to 10.3 in treated rats. In human urine, measurements could easily be made in 2 ml of urine in females, but in males much larger volumes were required due to the low levels of sphingolipid bases.     

Epididymo-orchitis and Reiter''s disease. Two infrequent complications after intravesical bacillus Calmette-Guérin therapy

Two cases of adverse reactions to intravesical treatment with bacillus Calmette-Guérin are reported. The first patient presented with a severe suppurating epididymo-orchitis three months after his last treatment. The second patient developed Reiter's disease with arthritis of one knee and conjunctivitis 1 week after the fourth instillation.     

The cement mantle in the Exeter impaction allografting technique. A cause for concern

The postoperative radiographs of 35 patients who underwent impaction allografting of the proximal femur were reviewed. Of Gruen zones that could be clearly visualized, 39.9% contained areas where cement was absent. Even when an adequate mantle was present, cement voids were commonly seen. These cement mantle deficiencies were confirmed in a series of cadaveric impaction allografting procedures. They appear to be a consequence, at least in part, of an inadequate differential between trial and actual component sizes. Additionally, 4 patients were identified with significant component migration secondary to radiographically visible cement mantle fractures within the first 6 months of surgery. It is concluded that the surgical technique requires modification to ensure a more consistent cement mantle and clinical result.     

Small bowel transplantation: current progress and clinical application

Total parenteral nutrition (TPN) is used routinely to maintain patients with the Short Bowel Syndrome (SBS). Until recently, TPN has been the only available therapeutic modality for patients with SBS. Currently, it is the treatment of choice for such individuals and occasionally, when the loss of bowel is extensive, it may be the only way of maintaining life. Unfortunately, TPN is expensive and markedly restrains an individual's lifestyle. Despite the overall success of TPN, the numerous risks associated with its use and the many complications of having an intravenous indwelling for years have served as the stimulus for alternative treatments such as small bowel transplantation (SBT). The first attempts at small bowel transplantation in clinical medicine were by Detterling almost 25 years ago. Patient death or graft loss in these early attempts was caused by the failure to control graft rejection and/or the inability to prevent Graft Versus Host Disease (GVHD). A stimulus for renewed clinical interest in SBT was provided by Starzl et al in 1988 with a report of prolonged graft survival without graft rejection or GVHD in a patient who was the recipient of a multivisceral graft consisting of the entire small bowel and other abdominal organs. Since 1964, 78 Small Bowel transplants have been performed in humans. Several variations of the multivisceral procedure in which the liver and the small bowel constitute the major components of the graft were adopted. The longest survival has been in a child who is still alive with a working graft for more than two years, as reported by Goulet from Paris in 1989. The introduction in SBT of the new immunosuppressive agent FK 506 had provided results which are superior to those achieved with Cyclosporine A (CsA). This latter observation prompted the Pittsburgh group to initiate a large series of isolated and composite intestinal grafts. The remarkable results have demonstrated the clinical utility of intestinal transplantation. This paper will try to summarize the history of the small bowel transplantation until the end of the year 1992, with the current progress in use today.     

Bit error simulation for π/4 DQPSK mobile radio communicationsusing two-ray and measurement-based impulse response models

An accurate software/hardware bit-by-bit error simulator for mobile radio communications is described. Simulation results in indoor and outdoor channels are compared with theoretical results. Bit error rate (BER) results in simulated frequency-selective fading channels generated by several channel models such as two-ray, constant amplitude, and simulated indoor radio channel impulse models (SIRCIMs) are presented. It is shown that BER is not only dependent on the RMS delay spread, but also on the distribution of temporal and spatial multipath components in local areas. An important result is that a two-ray Rayleigh fading model is a poor fit for indoor wireless channels and, if used, can underestimate the BER by orders of magnitude. A real-time bit error simulation of video transmission using the bit-by-bit error simulator is described. The simulator, called BERSIM, is shown to be a useful tool for evaluating emerging data transmission products for digital mobile communications     

Comparison of calcium phosphate cement mixture and pure calcium hydroxide as direct pulp-capping agents

This review reports the different genetic factors that have been identified either as risk factor for Alzheimer's disease (AD) or directly causing the disease. First are reviewed epidemiological data and biological mechanisms about the apoplipoprotein E gene allele epsilon 4 that is a major risk factor for Alzheimer's disease. The second part describes the mutations responsible for early-onset autosomal dominant AD found in three different genes. The gene located on chromosome 21 encodes the amyloid precusor protein (APP). The presenilin 1 and presenilin 2 genes, located on chromosome 14 and 1 respectively, encode not yet known membrane proteins.     

Extrapolated galerkin time finite elements

A new time finite-element method based on the extrapolation technique and the Galerkin time finite-element method is presented. In this method, the second-order governing differential equations of motion for dynamic problems are rewritten as a set of first order differential equations in state space. The standard Galerkin method is then employed for the temporal discretization. The algorithm is first-order accurate only. Based on the first-order Galerkin time finite-element formulation, the extrapolation technique is introduced to improve the order of accuracy. It is achieved by expressing the numerical amplification matrix of higher-order algorithm as a linear combination of the basic amplification matrices evaluated at selected instances of time. The matrices are combined with different weighting factors. The pairs of the selected instance of time and the corresponding weighting factors are free parameters. Unconditionally stable higher-order accurate formulations can be derived by properly choosing the free parameters. Algorithms up to fourth-order accurate are presented in this paper. Detailed analyses on stability, numerical dissipation and numerical dispersion are also given. Comparisons of the present algorithms with some well-known time-integration methods are presented to demonstrate the versatility of the present method, in particular its accuracy in the higher-order formulations.     

Localization by immunoelectron microscopy of Schistosoma mansoni antigens in the glomerulus of the hamster (Mesocricetus auratus) kidney

Gene therapy has the potential to provide cancer treatments based on novel mechanisms of action with potentially low toxicities. This therapy may provide more effective control of loco-regional recurrence in diseases such as non-small cell lung cancer (NSCLC), as well as systemic control of micrometastases. Despite current limitations, retroviral and adenoviral vectors can in certain circumstances provide an effective means of delivering therapeutic genes to tumour cells. Although multiple genes are involved in the process of carcinogenesis, mutations of the p53 gene are the most frequent abnormality identified in human tumours. Pre-clinical studies both in vitro and in vivo have shown that restoration of p53 function can induce apoptosis in cancer cells. Phase I clinical trials now show that p53 gene replacement therapy is feasible and safe using both retroviral and adenoviral vectors, and that it induces tumour regression in patients with advanced NSCLC and recurrent head and neck cancer. Other pre-clinical studies indicate that gene therapy may have useful synergy with cytotoxic and radiation therapy. This paper describes the different gene therapy strategies under investigation and the pre-clinical data that provides a rationale for the gene replacement approach, reviews clinical trial data and presents novel ideas for improving current vectors and gene delivery to tumours.