Immunogenetic considerations in islet transplantation: The role of Ia antigens in graft rejection

As demonstrated by Faustman et al., islets that are pretreated with Ia antibodies and complement show markedly prolonged survival as compared with islets, with the same immunogenetic disparity, without antibody pretreatment. In order to test whether it is simply the absence of an allo-Ia disparity that accounts for this finding, we have transplanted islets across class I disparities alone; in certain cases, such islets are rapidly rejected. Yet, even though there is no allo-Ia difference on such islets, pretreatment of the islets with anti-Ia monoclonal antibody also results in markedly prolonged survival. We suggest that the presence of Ia antigens may serve as a differentiation marker for cells that can present class I antigens in an immunogenic manner; further, allo-Ia antigens can lead to a stronger anti-class I rejection response.     

Haemodynamics in acute arthritis of the knee in puppies

In order to study the haemodynamic changes of the juvenile knee in acute arthritis, an experimental model was developed in puppies by unilateral intra-articular injections of Carragheenin solution into the knee. Tissue blood flow was studied by the tracer microsphere technique in eight dogs and simultaneous intra-articular and intraosseous pressure recordings were performed in seven other dogs. The intra-articular pressure was elevated in all arthritic knees. Hyperaemia was found in the knee-joint capsule and distal femoral metaphysis, whereas juxta-articular epiphyseal blood flow rates were not significantly changed. A decrease of femoral muscle blood flow was encountered. Intraosseous pressure recordings during venous tamponade of the knee-joint capsules suggested a qualitative change of bone vasculature in acute arthritis. The juxta-articular bone blood flow in arthritis appears to be influenced by synovial hyperaemia, synovial effusion pressure, an "inflammatory resistance factor" and the anatomical relationship of the epiphyseal vessels to the knee-joint capsule.     

When the universal is particular: a re-examination of the common morality using the work of Charles Taylor

Medicine, Health Care and Philosophy - Beauchamp and Childress’ biomedical principlism is nearly synonymous with medical ethics for most clinicians. Their four principles are theoretically...     

Variability of the steady-state visually evoked potential: Interindividual variance and intraindividual reproducibility of spatial frequency tuning

At low contrast levels there is good agreement between the psychophysical contrast sensitivity function and the tuning curve of the visually evoked potential (i.e., VEP amplitude vs spatial frequency). At high contrast, however, some researchers have found bimodal VEP tuning curves whereas others have not. We studied the VEP in 22 subjects in a short-term cross-sectional study and in 13 subjects in a longitudinal study over 8 sessions covering 28 days. Grating stimuli with 60% contrast were square-wave modulated in time (7.8 reversals/s) and space (0.06–16 cycles/degree). We found large interindividual variance in the shape of the tuning curves; about half of the subjects showed a unimodal shape, while the other half showed a bimodal one (with a notch between 1 and 2 cycles/degree). These features turned out to be stable in the longitudinal study, where variability could mainly be ascribed to a multiplicative influence common to all spatial frequencies. The marked interindividual differences in the shape of the tuning curve, which seem to be intraindividually stable, may explain previous discrepancies. It is not yet clear why the notch exists in about half of our subjects.     

Methadone dosing, heroin affordability, and the severity of addiction

OBJECTIVES: This study sought to track changes in US heroin prices from 1988 to 1995 and to determine whether changes in the affordability of heroin were associated with changes in the use of heroin by users seeking methadone treatment, as indexed by methadone dose levels. METHODS: Data on the price of heroin were from the Drug Enforcement Administration; data on methadone doses were from surveys conducted in 1988, 1990, and 1995 of 100 methadone maintenance centers. Multivariable models that controlled for time and city effects were used to ascertain whether clinics in cities where heroin was less expensive had patients receiving higher doses of methadone, which would suggest that these patients had relatively higher physiological levels of opiate addiction owing to increased heroin use. RESULTS: The amount of pure heroin contained in a $100 (US) purchase has increased on average 3-fold between 1988 and 1995. The average dose of methadone in clinics was positively associated with the affordability of local heroin (P < .01). CONCLUSIONS: When heroin prices fall, heroin addicts require more methadone (a heroin substitute) to stabilize their addiction--evidence that they are consuming more heroin.     

Cost-effectiveness analysis in anaesthesia

In order to preserve the quality of anaesthetic care under cost containment programmes, the concept of value-based anaesthesia was introduced. To achieve this goal, namely, the provision of the best possible care attainable at a reasonable cost, studies are necessary that compare anaesthetic techniques in terms of both quality and costs, e.g. by means of cost-effectiveness analyses.     

Cell subsets responding to purified hepatocytes and evidence of indirect recognition of hepatocyte major histocompatibility complex class I antigen. I. The role of L3T4+ T cells in the development of allospecific cytotoxicity in hepatocyte-sponge matrix allografts.

The purpose of this study was to determine the role of L3T4+, Ly2- T cells in the development of allospecific cytolytic T cells in response to purified allogeneic MHC class I+, class II- hepatocytes in vivo in hepatocyte-sponge matrix allografts (HC-SMA). In previous studies we have shown that 99% pure murine hepatocytes stimulate the development of allospecific cytolytic T cells in vitro in mixed lymphocyte-hepatocyte culture (MLHC) and in vivo in HC-SMA. Furthermore, depletion of L3T4+, Ly2- T cells from responder splenocytes inhibits the development of allo-CTLs in response to purified hepatocytes in mixed lymphocyte-hepatocyte culture. Here, using an anti-L3T4 monoclonal antibody, we tested the effect of in vivo immunodepletion of L3T4+, Ly2- T cells on the subsequent development of allo-CTLs in HC-SMA. Sponge cells were harvested on day 4 and day 12 after grafting from control and treated groups and phenotypically analyzed by FACS and immunofluorescent labelling. Splenocytes from the same animals were similarly analyzed to assess for completeness of immunodepletion. Allospecific cytotoxicity was assessed on day 12 after grafting. We found that immunotherapy with anti-L3T4 mAb was effective in depleting L3T4+, Ly2- T cells from the spleen; however, a similar number of L3T4+ cells was isolated from the sponge between control and treated groups. Furthermore, the development of allo-CTLs in response to hepatocytes in HC-SMA was completely abrogated by both local and systemic immunotherapy with anti-L3T4 mAb. We conclude from these and previous data that host or responder L3T4+, Ly2- T cells and responder accessory cells in MLHC or host macrophages in HC-SMA may participate in "indirect" recognition of hepatocyte class I antigen both in vitro and in vivo.