Conventional drug therapy in inflammatory bowel disease

The conventional treatment of inflammatory bowel disease should center around the liberal use of one of the many available forms of 5-ASA. Sulfasalazine should be used initially with the newer mesalamine-only containing drugs being reserved for sulfasalazine-intolerant patients or for those patients who require larger doses of medication. The choice of the delivery method should be made with the knowledge of the extent of disease and the potential coverage areas of the individual delivery methods. Systemic and topical glucocorticoids are an invaluable adjunct to 5-ASA therapy, but their use must be directed with the goal of remission induction. The tapering of glucocorticoids should be as prompt as the maintenance of remission allows, with a useful general guideline of decreasing the dose by 1 mg per day. Immunosuppressive therapy, including azathioprine and 6-mercaptopurine, holds promise for refractory cases of inflammatory bowel disease and for their potential steroid sparing properties; antibiotic therapy with metronidazole and ciprofloxacin in the absence of documented infectious disease offers additional routes to control disease. The majority of patients require a combination of drugs to attain remission. Only further study will reveal the ideal regimen for each of the different subsets of inflammatory bowel disease.     

Detecting delaminations in a composite beam using anti-optimization

The present study proposes a detection technique for delaminations in a laminated beam. The proposed technique optimizes the spatial distribution of harmonic excitation so as to magnify the difference in response between the delaminated and intact beam. The technique is evaluated by numerical simulation of two-layered aluminum beams. Effects of measurement and geometric noise are included in the analysis. A finite element model for a delaminated composite, based on a layer-wise laminated plate theory is used in conjunction with a step function to simulate delaminations     

Differential activity of the G protein beta5 gamma2 subunit at receptors and effectors

The G protein beta5 subunit differs substantially in amino acid sequence from the other known beta subunits suggesting that beta gamma dimers containing this protein may play specialized roles in cell signaling. To examine the functional properties of the beta5 subunit, recombinant beta5 gamma2 dimers were purified from baculovirus-infected Sf9 insect cells using a strategy based on two affinity tags (hexahistidine and FLAG) engineered into the N terminus of the gamma2 subunit (gamma2HF). The function of the pure beta5 gamma2HF dimers was examined in three assays: activation of pure phospholipase C-beta in lipid vesicles; activation of recombinant, type II adenylyl cyclase expressed in Sf9 cell membranes; and coupling of alpha subunits to the endothelin B (ETB) and M1 muscarinic receptors. In each case, the efficacy of the beta5 gamma2HF dimer was compared with that of the beta1 gamma2HF dimer, which has demonstrated activity in these assays. The beta5 gamma2HF dimer activated phospholipase C-beta with a potency and efficacy similar to that of beta1 gamma2 or beta1 gamma2HF; however, it was markedly less effective than the beta1 gamma2HF or beta1 gamma2 dimer in its ability to activate type II adenylyl cyclase (EC50 of approximately 700 nM versus 25 nM). Both the beta5 gamma2HF and the beta1 gamma2HF dimers supported coupling of M1 muscarinic receptors to the Gq alpha subunit. The ETB receptor coupled effectively to both the Gi and Gq alpha subunits in the presence of the beta1 gamma2HF dimer. In contrast, the beta5 gamma2HF dimer only supported coupling of the Gq alpha subunits to the ETB receptor and did not support coupling of the Gi alpha subunit. These results suggest that the beta5 gamma2HF dimer binds selectively to Gq alpha subunits and does not activate the same set of effectors as dimers containing the beta1 subunit. Overall, the data support a specialized role for the beta5 subunit in cell signaling.     

Genetic control of immunity to Heligmosomoides polygyrus: presentation of promiscuous antigens to parasite-specific T cell hybridomas

The role of MHC class II in the presentation of Heligmosomoides polygyrus antigens has been investigated, using a number of T cell hybridomas produced in A and E positive and negative mice. By using fixed and irradiated antigen presenting cells (APC), further evidence has emerged, to support earlier data, that there can be differential processing requirements during the presentation of H. polygyrus antigens by A and E molecules. In concordance with these earlier observations, this work provides further evidence than individual T cells can respond to antigen when presented by more than one MHC molecule. Previously, this evidence has been restricted to individual MHC molecules of the same haplotype, but these data show that H. polygyrus produces antigens which can be presented by both syngeneic and allogeneic MHC molecules. These antigens do not appear to be synonymous with the previously described H. polygyrus superantigen, as presentation is restricted to specific MHC haplotypes. It is proposed that H. polygyrus may produce these antigenic molecules as part of its strategy to manipulate the host immune system.     

Foundations'' impact on policy making: results from a pilot study

Thirty-two consecutive patients with haematological disorders, in need of a permanent central venous catheter (CVC) were randomly allocated to have their CVC bandages (Tegaderm) changed once (OAW, n = 20) or twice (TAW, n = 19) a week. The two randomization arms were balanced in respect of age, sex, and underlying disease. The exit site of the CVC was inspected daily through the transparent bandage and erythema was noted. If severe erythema occurred, daily wet gauze dressings were applied. Samples for bacterial cultures were taken from the exit site of the CVC at every change of bandages. There was no difference in complications leading to removal of the CVC between the two groups (7/20 OAW vs. 7/19 TAW) or in CVC survival-time (P = 0.4). However, the OAW group had more positive CVC tip cultures (OAW 11/14 vs. TAW 2/9; P < 0.05) and a tendency to: (i) more extra dressings (P = 0.08); (ii) more cultures from the exit skin site showing high numbers of colony forming units (P = 0.07); (iii) shorter time to first exit site infection (P = 0.09); and (iv) more Gram-positive septicaemias (P = 0.08). Both clinical and bacteriological data in this study indicate that changing transparent polyurethane CVC bandages twice a week is superior to once a week.     

Multigigabit/s demultiplexing in optical domain using coherence properties of pulse trains from multiple, asynchronous mode-locked lasers

It is shown that the unique coherence properties of mode-locked lasers can be exploited to provide new opportunities for high-speed data transmission. Using passive Mach-Zehnder optical delay stages, very high bit rate optical data streams constructed from asynchronously combined transmitters can be demultiplexed directly in the optical domain, without imposing restrictions on the source wavelength. Potential implementation and performance of the technique are discussed.<>