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N-acetylmuramyl-L-alanyl-D-isoglutamine, or muramyl dipeptide (MDP), has been shown to be the minimal structure necessary for adjuvant activity. This compound can replace whole mycobacteria in Freund's complete adjuvant. In our continuing investigation of bacterial cell wall fragments of biological and immunotherapeutic interest, the necessity of obtaining MDP analogs of varying structure has proven to be of primary importance. We have found that the published routes to MDP could be effectively shortened to four steps starting from commercially available starting materials. As an example of this scheme, synthesis of the seryl analog will be detailed. gamma-benzyl glutamic acid could be elaborated in one step to the N-tertiary butoxycarbonyl seryl-gamma-benzyl isoglutamine. Deprotection of the Boc group followed by condensation with 1-O-benzyl-4, 6-O-benzylidine N-acetyl muramic acid provided the protected MDP. Deprotection of this product by hydrogenolysis gave the final product. Physical chemical and biological data as proof of structure is presented. Utility of these compounds in the line-10 tumor system is demonstrated.

A high incidence of tumor regression was observed in guinea pigs bearing transplantable, line-10 hepatocellular carcinomas when synthetic muramyl dipeptides combined with trehalose dimycolate in oil-in-water emulsions were injected directly into the tumors. These compounds are promising candidates to replace viable bacillus Calmette-Guérin in cancer immunotherapy in humans and animals.

The effects of two aminobutyryl and four seryl analogs of the synthetic muramyl dipeptide (MDP) against aerosol infections with influenza virus and Mycobacterium tuberculosis were studied. Regardless of the MDP analog employed, there was no evidence that the resistance against viral and bacterial aerosol infections was enhanced in the treated mice. In parallel studies, significant protection against influenza virus and M. tuberculosis infections was induced by the combination of MDP or analogs with the mycobacterial glycolipid trehalose dimycolate (TDM). Resistance conferred by the MDP + TDM combination against influenza virus was present 1 week after pretreatment and could be abrogated by macrophage inhibitory agents silica, dextran sulfate, and carrageenan. Splenic cells from MDP + TDM-pretreated animals generated markedly enhanced levels of luminol-dependent chemiluminescence in response to influenza A and B viruses.

Successful surgical treatment of a mycotic abdominal aortic aneurysm infected with Mycobacterium bovis is described. The infecting organism can be traced to an intraneoplastic injection of bacille Calmette-Guérin (BCG) vaccine into a cutaneous malignant melanoma nodule 14 months before aneurysm detection (17 months before operation). Treatment consisted of aneurysm excision, in situ prosthetic graft placement, and antituberculous medications. This patient represents the first reported case of BCG-induced mycotic aortic aneurysm.

We described elsewhere that the synergistic antitumor activity of endotoxic extracts from Re mutants of gram-negative bacteria and trehalose mycolate against guinea pig syngeneic line 10 tumor was abrogated after peptide substances accompanying these extracts had been removed. This activity could be restored by combining peptide-free endotoxin either with cell wall skeleton from Bacillus Calmette-Guérin, a polymeric mycolic acid-arabinogalactan-mucopeptide complex, or with a combination of two separate components, trehalose dimycolate and N-acetylmuramyl-L-alanyl-(L-seryl)-D-isoglutamine (MDP). We report here that when a combination of endotoxin (150 microgram) and a mixture of MDP (150 microgram) and trehalose dimycolate (150 microgram) was inoculated into established dermal tumors, a significant number of the animals died, presumably of endotoxic shock. All surviving animals suffered severe but temporary lethargy. When administered alone intradermally in the dose levels tested, none of the components caused severe lethargy or lethality. The lethal effects of 159 microgram of MDP also occurred in combination with relatively weak endotoxic products, such as Pseudomonas vaccine (Pseudogen), and these effects did not depend upon the presence of malignant tissue. Guinea pigs inoculated i.v. were even more susceptible inasmuch as the addition of as little as 6 microgram of MDP to 150 microgram of Pseudogen, itself not lethal, caused the death of 80% of the animals.

This paper has been concerned with a patient's problematic behavior pattern, namely hallucinations. The social and dynamic significance of the behavior for the individual have been explored and analyzed and a formulation of possible developmental processes influencing the patient to utilize hallucinations has been discussed. On the basis of these analyses, formulations for a psychiatric nursing treatment plan of intervention have been presented. In conclusion, it is well to bear in mind that the schizophrenic patient, who is hallucinating, is striving to communicate in as clear and straightforward a way as he knows, the nature of his anxieties and experiences, despite how radically different they are from the nurse's, with speech content that is diffucult to follow. Thus, with this understanding, it behooves us as nurses to intervene accordingly and "decode" the hallucinated messages and thereby assist in breaking into the third stage in the evolutionary cycle of a psychosis, as cited by R.D. Laing: Stage 1 = Good (me); Stage 2 = Bad (me); Stage 3 = Mad (not me).

The present study was designed to evaluate the effect of an intensive physical training program involving both isometric and isotonic activities on the body iron status of 8 females and 11 males (age 20 +/- 1 year). The training was carried out over a 7 week period and included 8 h of varying physical activities each day. Venous blood samples were obtained from the subjects prior to the beginning of the training, on day 2 and in weeks 2, 4, 6 and 7 of the program. Blood samples were analyzed for iron, ferritin and hemoglobin (Hb) concentrations, total iron binding capacity (TIBC) and red blood cell count (RBC). Iron levels of males and females decreased 65% after 2 weeks of training (p less than 0.001). At the end of the training program 5 males and 6 females had lower than normal iron values (less than 13.4 mumol.l-1). TIBC increased 25% in women and 18% in men following 2 and 4 weeks of training (p less than 0.001) and remained at this elevated level throughout the training period. Ferritin levels decreased 50% in both sexes after 4 weeks of exercise (p less than 0.05) and remained at this level until the end of the training. Hb and RBC decreased 8-10% in both sexes during the training period. In two of the women anemia occurred after 4 weeks of training. The development of latent iron deficiency in a substantial number of participants after a relatively short period of training is uncommon and may reflect the high intensity of exercise required in this program.(ABSTRACT TRUNCATED AT 250 WORDS)

Ureterosigmoidostomy can be complicated by pyelonephritis, renal calculi, hypokalemic hyperchloremic acidosis, and colonic neoplasia. It has been associated with the development of hyperammonemia and encephalopathy in patients with underlying liver disease. We report a rare case of hyperammonemic encephalopathy in a patient with normal liver function.