Liposomal amikacin: improved treatment of Mycobacterium avium complex infection in the beige mouse model.

Disseminated Mycobacterium avium complex (MAC) infection has reached epidemic proportions and is a major cause of morbidity and mortality in AIDS patients. We have developed a liposomal preparation of amikacin, VS107, which incorporates the drug in 54-65 nm diameter unilameller phospholipid vesicles and is stable at 4 degrees C for more than 4 months. VS107 exhibits superior microbiological and pharmacological activity over the free amikacin and improves the survival of mice in the established model for MAC infection. The serum half-life of VS107 in mice was 9.1 h and a peak serum level of 730 mg/L was obtained after administering three doses of 160 mg/kg. For the therapeutic study, beige mice infected with 10(7) cfu M. avium complex strain 101 were randomised to be treated with placebo liposomes, buffer, free amikacin or VS107 The drugs were administered via the caudal vein thrice weekly for 1, 3, 5 or 7 weeks beginning 5 days after infection. After 51 days of treatment with VS107, the number of viable M. avium in the liver and spleen was a 100 fold lower than was achieved with conventional amikacin (P < 0.01), and more than six decimal logarithms lower than was found untreated controls (P < 0.001). VS107 was well tolerated and might be a suitable candidate for treating human MAC infections.

Experimental murine infection with the diffuse cutaneous leishmaniasis strain, Isabel.

Infection with the Isabel strain of Leishmania has been followed in several inbred strains of mice over an extended period. The mouse strains segregate into three major types with respect to susceptibility to infection: BALB/c, BALB.B and SWR/J are susceptible; DBA/1J is intermediate; and C57BL/6, C57BL/10, DBA/2J and B10.D2 are resistant. Infections with other leishmanial strains have been well-characterized in the BALB/c mice. Therefore, BALB/c mice were selected for extended studies. Progression of the disease was assessed by the following parameters: (1) numbers of parasites isolated from various tissues including footpad lesions, spleens, and lymph nodes and (2) the presence of metastatic lesions. This model should prove valuable in the study of the early immunological events in leishmaniasis.

Recent advances in the behavioral treatment of obsessive-compulsives.

The last decade has witnessed remarkable progress in the treatment of obsessive-compulsives, with the introduction of response prevention and deliberate exposure to feared situations in vivo and in imagination. In a series of studies, the effects of the single components of this program were investigated. The results suggest that the optimal treatment includes a combination of all three procedures. It appears that in vivo exposure mainly affects anxiety/discomfort associated with cues for ritualizing; response prevention affects primarily compulsive behavior; and imaginal exposure assists in maintenance of treatment gains, perhaps through its impact on fears of future catastrophes associated with obsessions.

Relaxation treatment of pseudoinsomnia and idiopathic insomnia: an electroencephalographic evaluation.

Twenty-nine insomniacs underwent four consecutive sleep laboratory evaluations before and after receiving tension-release relaxation training, no-tension-release relaxation training, or no-treatment. On the basis of the discrepancy between subjective and EEG-defined measures of latency to sleep onset, subjects were classified as pseudoinsomniacs or idiopathic insomniacs. As predicted, tension-release relaxation was significancy more effective than the other two conditions on subjective sleep measures, regardless of insomnia subtype and on objective sleep measures only for idiopathic insomniacs. Subjective improvement was maintained at 12-month followup. Numerous differences between the two subtypes emerged on pretherapy and during-therapy measures distinct from the latency measures, but changes on those variables were unrelated to outcome improvement.