Villa of Publius Fannius Synistor, interior, Cubiculum (Bedroom) M, left wall

Boscoreale, Italy; fresco

Krater, left side

Hirschfeld Workshop, attributed to; 3 ft. 6 41/64 in.x 2 ft. 4 1/2 in.; terracotta

Portrait of the Emperor Caracalla, left side

Sculpture, Roman, Late Imperial; H: 1 ft. 1 1/2 in.; copper alloy

Everyday gourmet, with a section Left with a leftover.

Mode of access: Internet.

Left end Edwards /

Mode of access: Internet.

Finches and Bamboo: bird at left

Emperor Huizong; handscroll, ink and color on silk

Flowers and Birds of the Four Seasons, left scroll

Ikeda Koson; 3 ft. 6 13/32 in.x 1 ft. 2 11/64 in.; one of a pair of hanging scrolls, ink, color and gold on silk

Scenes in and around the Capital (Rakuchu-rajugai zu), left screen

Painting, Japanese, Edo; 5 ft. 1 29/64 in.x 11 ft. 6 21/32 in.; one of a pair of six-fold screens, ink, color, gold, and gold leaf on paper

Irises at Yatsuhashi (Eight Bridges), left screen

Ogata Korin; 5 ft. 10 33/64 in.x 12 ft. 2 17/64 in.; one of a pair of six-fold screens, ink and color on gold leaf on paper

Landscapes with the Chinese Literati Su Shi and Tao Qian, left screen

Nagasawa Rosetsu; 5 ft. 7 41/64 in.x 12 ft. 2 47/64 in.; one of a pair of six-fold screens, ink on gold leaf paper

Irises at Yatsuhashi (Eight Bridges), left screen: upper left

Ogata Korin; one of a pair of six-fold screens, ink and color on gold leaf on paper

Not left, not right, but forward.

Mode of access: Internet.

Which: the right, or the left?.

Pagi iii incorrectly numbered 3.

A convergent solution-phase synthesis of the macrocycle Ac-Phe-[Orn-Pro-D-Cha-Trp-Arg], a potent new antiinflammatory drug

Relatively few cyclic peptides have reached the pharmaceutical marketplace during the past decade, most produced through fermentation rather than made synthetically. Generally, this class of compounds is synthesized for research purposes on milligram scales by solid-phase methods, but if the potential of macrocyclic peptidomimetics is to be realized, low-cost larger scale solution-phase syntheses need to be devised and optimized to provide sufficient quantities for preclinical, clinical, and commercial uses. Here, we describe a cheap, medium-scale, solution-phase synthesis of the first reported highly potent, selective, and orally active antagonist of the human C5a receptor. This compound, Ac-Phe[Orn-Pro-D-Cha-Trp-Arg], known as 3D53, is a macrocyclic peptidomimetic of the human plasma protein C5a and displays excellent antiinflammatory activity in numerous animal models of human disease. In a convergent approach, two tripeptide fragments Ac-Phe-Orn-(Boc)-Pro-OH and H-D-Cha-Trp(For)-Arg-OEt were first prepared by high-yielding solution-phase couplings using a mixed anhydride method before coupling them to give a linear hexapeptide which, after deprotection, was obtained in 38% overall yield from the commercially available amino acids. Cyclization in solution using BOP reagent gave the antagonist in 33% yield (13% overall) after HPLC purification. Significant features of the synthesis were that the Arg side chain was left unprotected throughout, the component Boe-D-Cha-OH was obtained very efficiently via hydrogenation Of D-Phe with PtO2 in TFA/water, the tripeptides were coupled at the Pro-Cha junction to minimize racemization via the oxazolone pathway, and the entire synthesis was carried out without purification of any intermediates. The target cyclic product was purified (>97%) by reversed-phase HPLC. This convergent synthesis with minimal use of protecting groups allowed batches of 50100 g to be prepared efficiently in high yield using standard laboratory equipment. This type of procedure should be useful for making even larger quantities of this and other macrocyclic peptidomimetic drugs.

Left ventricular dyssynchrony predicts response and prognosis after cardiac resynchronization therapy

OBJECTIVES This study was designed to predict the response and prognosis after cardiac resynchronization therapy (CRT) in patients with end-stage heart failure (HF). BACKGROUND Cardiac resynchronization therapy improves HF symptoms, exercise capacity, and left ventricular (LV) function. Because not all patients respond, preimplantation identification of responders is needed. In the present study, response to CRT was predicted by the presence of LV dyssynchrony assessed by tissue Doppler imaging. Moreover, the prognostic value of LV dyssynchrony in patients undergoing CRT was assessed. METHODS Eighty-five patients with end-stage HF, QRS duration >120 ins, and left bundle-branch block were evaluated by tissue Doppler imaging before CRT. At baseline and six months follow-up, New York Heart Association functional class, quality of life and 6-min walking distance, LV volumes, and LV ejection fraction were determined. Events (death, hospitalization for decompensated HF) were obtained during one-year follow-up. RESULTS Responders (74%) and nonresponders (26%) had comparable baseline characteristics, except for a larger dyssynchrony in responders (87 +/- 49 ms vs. 35 +/- 20 ms, p < 0.01). Receiver-operator characteristic curve analysis demonstrated that an optimal cutoff value of 65 ms for LV dyssynchrony yielded a sensitivity and specificity of 80% to predict clinical improvement and of 92% to predict LV reverse remodeling. Patients with dyssynchrony :65 ms had an excellent prognosis (6% event rate) after CRT as compared with a 50% event rate in patients with dyssynchrony <65 ins (p < 0.001). CONCLUSIONS Patients with LV dyssynchrony greater than or equal to65 ms respond to CRT and have an excellent prognosis after CRT. (C) 2004 by the American College of Cardiology Foundation.