Organoindate room temperature ionic liquid: Synthesis, physicochemical properties and application

The combination of equimolar amounts of solid 1-n-butyl-3-methylimidazolum chloride (BMI-Cl) with solid indium trichloride affords the new room temperature and air stable ionic liquid BMI.InCl4 (mp -6 degreesC). The major physicochemical properties (density, viscosity, electrical conductivity and electrochemical window) of BMI.InCl4 are complementary to those of classical tetrafluoroborate or hexafluorophosphate analogues. However, this liquid possesses similar Lewis acidity properties to those of organoaluminate melts and can be used as recyclable media, as demonstrated here for the tetrahydropyranylation of alcohols.81155115

Tumor markers in breast cancer - European Group on Tumor Markers recommendations

Recommendations are presented for the routine clinical use of serum and tissue-based markers in the diagnosis and management of patients with breast cancer. Their low sensitivity and specificity preclude the use of serum markers such as the MUC-1 mucin glycoproteins ( CA 15.3, BR 27.29) and carcinoembryonic antigen in the diagnosis of early breast cancer. However, serial measurement of these markers can result in the early detection of recurrent disease as well as indicate the efficacy of therapy. Of the tissue-based markers, measurement of estrogen and progesterone receptors is mandatory in the selection of patients for treatment with hormone therapy, while HER-2 is essential in selecting patients with advanced breast cancer for treatment with Herceptin ( trastuzumab). Urokinase plasminogen activator and plasminogen activator inhibitor 1 are recently validated prognostic markers for lymph node-negative breast cancer patients and thus may be of value in selecting node-negative patients that do not require adjuvant chemotherapy. Copyright (C) 2005 S. Karger AG, Basel

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

On the identification of ionic species of neutral halogen dimers, monomers and pincer type palladacycles in solution by electrospray mass and tandem mass spectrometry

Electrospray (ESI) mass spectra analysis of acetonitrile solutions of a series of neutral chloro dimers, pincer type, and monomeric palladacycles has enabled the detection of several of their derived ionic species. The monometallic cationic complexes Pd[kappa(1) -C,kappa(1)-N, kappa(1)-S-C=(CH(3)S-2-C(6)H(4))C(Cl)CH(2)N(CH(3))(2)](+) (1a) and [Pd[kappa(1)-C,kappa(1)-N,kappa(1)-S-C=(CH(3)S-2-C(6)H(4))C(Cl)CH(2)N(CH(3))(2)](CH(3)CN)](+) (1b) and the bimetallic cationic complex [kappa(1)-C,kappa(1)-N,kappa(1)-S-C=(CH(3)S-2-C(6)H(4))C(Cl)CH(2)N(CH(3))(2)]Pd-Cl-Pd[kappa(1)-C,kappa(1)-N,kappa(1)-S-C=(CH(3)S2-C(6)H(4))C(Cl)CH(2)N(CH(3))(2)](+) (1c) were detected from an acetonitrile solution of the pincer palladacycles Pd[kappa(1)-C,kappa(1)-N,kappa(1)-S-C=(CH(3)S-2-C(6)H(4))C(Cl)CH(2)N(CH(3))(2)](Cl) 1. For the dimeric compounds {Pd[kappa(1)-C,kappa(1)-N-C=(Y-2-C(6)H(4))C(Cl)CH(2)N(CH(3))(2)](mu-Cl)}(2) (2, Y = H and 3, CF(3)), highly electronically unsaturated palladacycles [Pd[kappa(1)-C,kappa(1)-N-C=(Y-2-C(6)H(4))C(Cl)CH(2)N(CH(3))(2)](+) (2d, 3d) and their mono and di-acetonitrile adducts, namely, [Pd[kappa(1)-C,kappa(1)-N-C=(Y-2-C(6)H(4))C(Cl)CH(2)N(CH(3))(2)](CH(3)CN)](+) (2e, 3e) and [Pd[kappa(1)-C,kappa(1)-N-C=(Y-2-C(6)H(4))C(Cl)CH(2)N(CH(3))(2)](CH(3)CN)(2)](+) (2f and 3f) were detected together with the bimetallic complex [Pd[kappa(1)-C,kappa(1)-N-C=(Y-2-C(6)H(4))C(Cl)CH(2)N(CH(3))(2)]-Cl-Pd[kappa(1)-C,kappa(1)-N-C=(Y-2-C(6)H(4))C(Cl)CH(2)N](CH(3))(2)](+) (2a, 3a) and its acetonitrile adducts [kappa(1)-C,kappa(1)-N-C=(Y-2-C(6)H(4))C(Cl)CH(2)N(CH(3))(2)](CH(3)CN)Pd-Cl-Pd[kappa(1)-C,kappa(1)-N-C=(Y-2-C(6)H(4))C(Cl)CH(2)N(CH(3))(2)](+) (2b, 3b) and [kappa(1)-C,kappa(1)-N-C=(Y-2-C(6)H(4))C(Cl)CH(2)N(CH(3))(2)](CH(3)CN)Pd-Cl-Pd[kappa(1)-C,kappa(1)-N-C=(Y-2-C(6)H(4))C(Cl)CH(2)N(CH(3))(2)(CH(3)CN)](+) (2c, 3c). The dimeric palladacycle {Pd[kappa(1)-C,kappa(1)-N-C=(CH(3)O-2-C(6)H(4))C(Cl)CH(2)N(CH(3))(2)](mu-Cl)}(2) (4) is unique as it behaves as a pincer type compound with the OCH(3) substituent acting as an intramolecular coordinating group which prevents acetonitrile full coordination, thus forming the cationic complexes [(C(6)H(4)(o-CH(3))C=C(Cl)CH(2)N(CH(3))(2)-kappaO,kappaC,kappaN)Pd](+) (4b), [(C(6)H(4)(o-CH(3)O)C=C(Cl)CH(2)N(CH(3))(2)-kappaO,kappaC,kappaN)Pd(CH(3)CN)](+) (4c) and [(C(6)H(4) (o-MeO)C=C(Cl)CH(2)N(CH(3))(2)-kappaO,kappaC,kappaN)Pd-Cl-Pd(C(6)H(4)(o-CH(3)O)C=C(Cl)CH(2)N(CH(3))(2)-kappaO,kappaC,kappaN)](+) (4a). ESI-MS spectra analysis of acetonitrile solutions of the monomeric palladacycles Pd[kappa(1)-C,kappa(1)-N-C=(Y-2-C(6)H(4))C(Cl)CH(2)N(CH(3))(2)](Cl)(PY) (5, Y = H and 6, Y = CF(3)) allows the detection of some of the same species observed in the spectra of the dimeric palladacycles, i.e., monometallic cationic 2d-3d, 2e-3e and {Pd[kappa(1)-C,kappa(1)-N-C=(Y-2-C(6)H(4))C(Cl)CH(3)N(CH(3))(2)](PY)}(+) (5a, 6a) and {Pd[kappa(1)-C,kappa(1)-N-C=(Y-2-C(6)H(4))C(Cl)CH(2)N(CH(3))(2)](CH(3)CN)(PY)}(+) (5b, 6b) and the bimetallic 2a, 3a, 2b, 3b, 2c and 3c. In all cationic complexes detected by ESI-MS, the cyclometallated moiety was intact indicating the high stability of the four or six electron anionic chelate ligands. The anionic (chloride) or neutral (pyridine) ligands are, however, easily replaced by the acetonitrile solvent. (C) 2004 Elsevier B.V. All rights reserved.35782349235

Report on a case of fibrogenesis imperfecta ossium and a possible new treatment option.

Fibrogenesis imperfecta is an extremely rare acquired progressive bone disorder of unknown etiology. In its course, normal bone architecture is replaced at sites by structurally unsound collagen-deficient tissue resulting in a disorganized bone structure and a skeleton that is radically susceptible to deformity and fracture. Herein, we report the case of a patient who had experienced constant bone pain and several spontaneous fractures since 1997. In 10 years' time with the sole exception of his skull, the disease affected the entire skeleton causing a significant decrease in height and progressive disablement. Laboratory findings included elevation of serum alkaline phosphatase and C-terminal telopeptide of type 1 collagen, with normal serum calcium, phosphate, 25-hydroxy-vitamin-D, and parathyroid hormone concentrations. Monoclonal gammopathy was present with no pathological plasma cells in bone marrow. Radiological and histological results were inconclusive suggesting either osteoporosis, osteomalacia, or Paget's disease and later on osteosclerosis. Treatment administered for the abovementioned conditions has proven to be of no effect. The findings eventually raised the possibility of fibrogenesis imperfecta ossium, which was confirmed by polarized light microscopy as well as transmission electron microscopy. The suggested therapy for the disease is melphalan that could not be initiated due to legal restrictions. Steroid monotherapy also reported to be moderately successful in one case resulted in no improvement. Paraproteinemia had been suggested not only to be a characteristic feature but also a possible etiological factor in this condition. In 2012, plasmapheresis was initiated monthly at the beginning, later on biweekly. In response, the patient's symptoms improved dramatically supporting the abovementioned theory