Catalytic reaction between adsorbed oxygen and hydrogen on Rh(111)

Abstract unavailable

Computer-guided concentration-controlled trials in autoimmune disorders

A randomized concentration-controlled clinical trial (RCCCT) is an alternate experimental design to the standard dose-controlled study. In a RCCCT, patients are randomly assigned to predefined plasma or blood drug concentration ranges (low, medium, and high). With the caveat that concentration ranges are sufficiently separated, this design should enhance the ability to discover important concentration response relationships. FK-506, a potent and promising immunosuppressive agent for prevention and treatment of graft rejection, has shown significant clinical activity in some immune-mediated disorders. To implement the RCCCT design, a novel FK-506 intelligent dosing system (IDS) was used to guide all doses to prospectively achieve the target concentration range specified in the study protocol. Patients enrolled in these trials suffered from a variety of autoimmune disorders, including multiple sclerosis, primary biliary cirrhosis, psoriasis, autoimmune chronic active hepatitis, and nephrotic syndrome. We observed excellent predictive performance of the IDS for all patients. The accuracy (mean prediction error) of the IDS was −0.022 ng/ml and the precision (standard deviation of the prediction error) was 0.119 ng/ml. Thus, the IDS is both accurate and reproducible for autoimmune patients. We conclude that the RCCCT design, guided by an accurate and precise IDS, is an informative and cost-effective approach for evaluation of efficacy and safety of effective but highly toxic agents. © 1993 Raven Press, Ltd., New York

A dog model for acetaminophen-induced fulminant hepatic failure.

The development of a large animal model of fulminant hepatic failure produced with acetaminophen that should be useful in the development and evaluation of potential medical therapies for the important clinical problem of fulminant hepatic failure is described. Acetaminophen in dimethyl sulfoxide (600 mg/ml) given as three subcutaneous injections, with the first dose (750 mg/kg body wt) being given at noon, the second dose (200 mg/kg body wt) being given 9 h later, and the third dose (200 mg/kg body wt) being given 24 h after the initial dose consistently produces fulminant hepatic failure in dogs. The dimethyl sulfoxide vehicle, injected intramuscularly, does not influence either animal survival or hepatic function in control-treated dogs. No deaths occur within the first 36 h. By 72 h after initial drug administration, the mortality is 90%. Histopathological and biochemical investigations demonstrate a high degree of hepatocellular necrosis in nonsurviving animals without appreciable damage to the kidneys, lungs, or heart. The drug schedule and preparation outlined avoids the administration of large volumes of vehicle and results in prolonged high levels of acetaminophen in the blood sufficient to induce severe hepatic injury. Ranitidine (120 mg/kg body wt i.m.) given 30 min before each acetaminophen dose significantly reduces the mortality and hepatic necrosis produced using this model. This model satisfies all criteria established by Miller et al. for the production of a suitable large animal model of fulminant acute hepatic failure

A dog model for acetaminophen-induced fulminant hepatic failure.

The development of a large animal model of fulminant hepatic failure produced with acetaminophen that should be useful in the development and evaluation of potential medical therapies for the important clinical problem of fulminant hepatic failure is described. Acetaminophen in dimethyl sulfoxide (600 mg/ml) given as three subcutaneous injections, with the first dose (750 mg/kg body wt) being given at noon, the second dose (200 mg/kg body wt) being given 9 h later, and the third dose (200 mg/kg body wt) being given 24 h after the initial dose consistently produces fulminant hepatic failure in dogs. The dimethyl sulfoxide vehicle, injected intramuscularly, does not influence either animal survival or hepatic function in control-treated dogs. No deaths occur within the first 36 h. By 72 h after initial drug administration, the mortality is 90%. Histopathological and biochemical investigations demonstrate a high degree of hepatocellular necrosis in nonsurviving animals without appreciable damage to the kidneys, lungs, or heart. The drug schedule and preparation outlined avoids the administration of large volumes of vehicle and results in prolonged high levels of acetaminophen in the blood sufficient to induce severe hepatic injury. Ranitidine (120 mg/kg body wt i.m.) given 30 min before each acetaminophen dose significantly reduces the mortality and hepatic necrosis produced using this model. This model satisfies all criteria established by Miller et al. for the production of a suitable large animal model of fulminant acute hepatic failure

Vergleich dreier Ringversuche zur radioimmunologischen Thyrotropin-Bestimmung nach dem "Münchner Modell"

Peer Reviewe

A versatile source of polarization-entangled photons

We propose a method for the generation of a large variety of entangled states, encoded in the polarization degrees of freedom of N photons, within the same experimental setup. Starting with uncorrelated photons, emitted from N arbitrary single photon sources, and using linear optical tools only, we demonstrate the creation of all symmetric states, e.g., GHZ- and W-states, as well as all symmetric and non-symmetric total angular momentum eigenstates of the N qubit compound.Comment: 4 pages, 3 figure

Monoclonal gammopathy after intense induction immunosuppression in renal transplant patients

Objectives. Incidence and risk factors of post-transplant monoclonal gammopathy were studied in renal transplant patients who received their grafts between 1982 and 1992 (n=390 grafts). Immunoelectrophoresis was performed at annual intervals after transplantation. Results. Forty-six cases of clonal gammopathy were detected: 35 monoclonal, 11 bi- or triclonal, with a predominance of IgG and K light-chain subtypes (IgG, 39; IgA, 3; IgM, 4; K, 35; λ, 19). Gammopathy was transient in 17 patients (37%). The 5-year cumulative incidence of gammopathy was 10.7%, much higher than expected for a group of similar age from the general population. Thirty of the 46 gammopathies appeared within the first 2 years of transplantation. Gammopathy never progressed to multiple myeloma during follow-up (median 1 year; (range 0-10)); one patient subsequently developed Kaposi sarcoma. The 2-year incidence of gammopathy was much higher in patients transplanted in 1989-1991 (23/142) than in 1982-1988 (7/248) (P<0.0001). This coincided with the use of quadruple induction immunosuppression (cyclosporin A+azathioprine+prednisone plus either ATG-Fresenius (ATG-F) or OKT3) since 1989. The risk for acquiring gammopathy within 2 years of transplantation was 14.7% (95% CI 9.2, 20.3%) in patients receiving quadruple induction therapy, but only 3.0% (CI 1.2, 6.1%) without such therapy (P<0.0001). The risk for patients receiving quadruple immunosuppression with OKT3 was 24.5%, significantly greater than with ATG-F (11.8%, P<0.05). Discriminant analysis revealed that the type of immunosuppression, but not age or year of transplantation, were independent risk factors for gammopathy. Conclusions. Monoclonal gammopathy frequently occurs after renal transplantation. Risks are higher for patients receiving quadruple induction immunosuppression, particularly if it includes OKT3. Follow-up of these patients is warranted for the early detection of malignant transformatio