IMPORTANT contributions to our knowledge and understanding of infective endocarditis were made by a number of students of this disease in the first third of this century. Thayer,1 among others, preferred the term infective endocarditis for this disorder, giving it equal emphasis with the more common designation bacterial endocarditis. We have chosen to employ Thayer's terminology because a significant aspect of the changing picture of this disease is an increasing involvement of agents such as fungi and even rickettsias; the term bacterial endocarditis, therefore, is not strictly applicable. In 1955 Kerr2 summarized all the significant information concerning subacute bacterial . . .

Infective endocarditis in the antibiotic era.

Morphine was demonstrated to exacerbate infections. Experiments were performed to evaluate variations of phagocytic physiology during morphine treatment. In mice, morphine drastically reduced reticuloendothelial system activity, phagocyte count, phagocytic index, killing properties, and superoxide anion production in polymorphonuclear leukocytes and macrophages. Similar effects on alveolar macrophage count, phagocytosis, and killing were found in rabbits, a result which suggested a lack of species specificity. Additional experiments demonstrated that morphine (1) induces a reduction of lymphoid organ weight, (2) impairs the ability to eradicate infections and (3) is counteracted in its depressing activity on phagocytic physiology by small amounts of Corynebacterium parvum. The results suggest that there is a close relationship between the fact that morphine exacerbates infections and the fact that morphine depresses phagocytic functions; therefore, the negative effect of morphine on phagocytosis is at least one of the reasons for its negative effect on the development of infections.

Effect of morphine on resistance to infection.

The narcotic addict as a medical patient

Laboratory data indicate that morphine decreases the number of peritoneal and alveolar macrophages (Mφ) and compromises their phagocytic capability for immune complexes and bacteria. We hypothesize that morphine decreases the number of, as well as compromises the phagocytic capability of, Mφ by programming their death. We studied the effect of morphine on Mφ apoptosis in vivo as well as in vitro. Peritoneal Mφ harvested from morphine-treated rats showed DNA fragmentation. Morphine enhanced murine Mφ (J 774.16) apoptosis in a dose-dependent manner. Human monocytes treated with morphine showed a classic ladder pattern in gel electrophoretic and end-labeling studies. Morphine promoted nitric oxide (NO) production both under basal and LPS-activated states. N G -nitro-l-arginine methyl ester (l-NAME) and N G -monomethyl-l-arginine monoacetate (l-NMMA), inhibitors of NO synthase, attenuated the morphine-induced generation of NO by Mφ. Morphine also enhanced Mφ mRNA expression of inducible NO synthase (iNOS). Since morphine-induced Mφ apoptosis was inhibited by L-NAME and L-NMMA, it appears that morphine-induced Mφ apoptosis may be mediated through the generation of NO. Morphine promoted the synthesis of Bax and p53 proteins by Mφ. Moreover, IL-converting enzyme (ICE)-1 inhibitor attenuated morphine-induced Mφ apoptosis. These studies suggest that morphine activates the induction phase of the apoptotic pathway through accumulation of p53. The effector phase of morphine-induced apoptosis appears to proceed through the accumulation of Bax and activation of ICE-1. The present study provides a basis for a hypothesis that morphine may be directly compromising immune function by promoting Mφ apoptosis in patients with opiate addiction.

Morphine Enhances Macrophage Apoptosis

Right-sided valvular infective endocarditis: A clinicopathologic study of twelve necropsy patients

THE possibility that intravenous injection of opium in addicts might serve as a means of entry for organisms that could cause endocarditis was suggested by Lutembacher 1 more than thirty years ago, when he wrote of " une injection intraveineuse malpropre ." A review of almost all the cases of endocarditis reported in English in the past thirty years, however, shows that venipuncture for the injection of opium or its derivatives was a possible factor in only 12 instances (table 1). An interesting group of 11 such cases, involving patients observed in a short period, forms the basis of this paper (table 2). METHOD OF ADMINISTRATION OF DRUG BY ADDICTS The method of administration of opium employed by addicts lends itself to the introduction of organisms into the blood stream. The equipment of an addict consists of an ordinary medicine dropper and a hypodermic needle, with a bit of cigaret paper

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William F. Luttgens

Papers

ENDOCARDITIS IN MAIN LINE OPIUM ADDICTS: Report on Eleven Cases