Diagnosing isolated cardiac sarcoidosis.

OBJECTIVES: Cardiac sarcoidosis (CS) without clinically apparent extracardiac disease may escape detection because of the poor sensitivity of endomyocardial biopsy (EMB). We set out to analyse our experience of repeated and imaging-guided biopsies in clinically isolated CS. METHODS: We retrospectively reviewed the medical records, laboratory test results, imaging studies and pathological analyses of 74 patients with either histologically proven or clinically probable CS at our institution between January 2000 and December 2010. RESULTS: Fifty-two patients had histologically proven CS, of whom 33 (26 women) had disease that was clinically isolated to the heart. Sarcoidosis was detected in the first EMB in 10 of the 31 patients who underwent biopsy. CS was found by repeated EMBs, targeted by cardiac imaging, in seven additional patients, and 11 patients were diagnosed by sampling 18-F-fluorodeoxyglucose position emission tomography-positive mediastinal lymph nodes at mediastinoscopy. Together, the first biopsy (cardiac or mediastinal lymph node) provided the diagnosis in 34%, the second biopsy in 31% and the third in 22% of biopsied patients with isolated CS. Four (13%) of the remaining diagnosis were made after cardiac transplantation and one in a patient who did not undergo biopsy) at autopsy after sudden cardiac death. CONCLUSIONS: Cardiac sarcoidosis may present without clinically apparent disease in other organs. At least two-thirds of patients remain undiagnosed after a single EMB session. The detection rate can be improved by repeated and imaging-guided cardiac or mediastinal lymph-node biopsies. Nevertheless, false-negative biopsy results remain a problem in CS patients with no apparent extracardiac disease.

Halo lipids. 10. Synthesis and cytostatic activity of O-alkylglycerophospho-L-serine analogs.

The synthesis of O-alkylglycerophospho-L-serine analogs is described, which represent a new class of cytostatically active agents based on phospholipids. The new compounds were obtained by conversion of O-alkylglycerophosphoric ester analogs by means of phospholipase D and by condensing O-alkylglycerophosphoric acid analogs with protected L-serine followed by the removal of protective groups of the resulting intermediates. The structure of the O-alkylglycerophospho-L-serines was confirmed by fast atom bombardment mass spectrometry. The compounds were found to inhibit the growth of Ehrlich ascites tumor cells in vitro. Half maximum inhibition was observed at concentrations between 7 and 15 microM. For the 1-O-alkyl-2-methoxy glycerophosphoserine only a higher value (30 microM) was found. With most of the substances tested growth was completely inhibited at a concentration of 40 microM.

Inhibition of proliferation of Ehrlich ascites carcinoma cells in vitro and in vivo by halogeno analogues of long chain acyl- and alkylglycerols.

A series of halogeno (chloro or fluoro) analogues of phospholipid precursors has been checked for their cytostatic activity both in vitro and in vivo. The compounds included monoacyl-, diacyl-, monoalkyldeoxyhalogenoglycerols and other acylhalogenoalkanols. Analogues of monoacylglycerols or monoalkylglycerols were found to have a strong inhibitory activity on the proliferation of Ehrlich ascites carcinoma cells in suspension culture. The compounds were also effective in vivo. Tolerable doses (e.g. 1/10 of the LD50) given i.p. only once on the first day after transplantation of EAC cells reduced the cell number on day 7 by 99% or increased the survival time about 4-fold. The in vivo efficacy or the ether derivatives was higher than that of the corresponding esters. However, most of the compounds so far investigated had no effect on the survival time or cell number after s.c. application. Moreover, there was no prolongation of the survival time of leukemia L1210 or L184 bearing mice. This shows that the systemic effects of most of the compounds are low and that they have to come into direct contact with tumour cells during application in order to be active. It is discussed whether theese compounds interfere more with the structure of the membrane than with membrane biosynthesis. However, at least in comparison to Tween 80 (which is of poorer cytostatic activity) they show only very low lytic effects on red blood cells.

Protein and RNA of human telomerase as targets for modified oligonucleotides.

Chimeric oligodeoxynucleotides containing phosphorothioate and N3'-->P5' phosphoramidate linkages were synthesized. These oligomers show a high inhibitory activity against human telomerase.