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Changes in the number of alpha 2 adrenoreceptors in the hippocampus, as measured by the specific binding of 3H-clonidine, were compared to changes in presynaptic alpha 2 adrenoreceptor function in electrically stimulated hippocampal slices. In dependent rats the specific binding of 3H-clonidine was reduced significantly. At 32 h after withdrawal binding began to return toward normal values, and at 72 h after withdrawal was significantly greater than that seen in saline-treated rats. In hippocampal slice experiments sensitivity to clonidine was significantly decreased in morphine-dependent animals and returned toward normal values after withdrawal. At 72 h after withdrawal, the sensitivity to clonidine of the presynaptic alpha 2 adrenoreceptor remained depressed although receptor density as measured in the binding studies was increased. This study suggests that the changes in the function of presynaptic alpha 2 adrenoreceptors might be important in the development of dependence upon morphine.

The minimal inhibiting concentrations (MIC) of ampicillin, trisulfapyrimidines, and various combinations of these drugs were determined for four clinical isolates of Nocardia asteroides on Mueller-Hinton agar. The combination of ampicillin and sulfonamides was found to be synergistic for three of the four isolates when an inoculum of 10(3) to 10(4) organisms per ml was used. (Synergism was defined as occurring when the MIC of each of the drugs in combination was one-quarter or less of the MIC of each drug alone.) All four isolates were inhibited by concentrations of the drugs in combination that were clinically achievable. Combined therapy with ampicillin and sulfonamides was used in four immunologically suppressed renal transplant patients who had pulmonary infection with N. asteroides. Clinical improvement was noted within 2 weeks in all patients, and the pulmonary infiltrates cleared by 6 months in three patients. One patient died from an unrelated illness 10 days after starting therapy. The disease was arrested in two patients who were maintained on full immunosuppressive therapy.

The effects produced by single and mixed infections with Mycoplasma pulmonis and influenza A/PR-8 virus were studied in mouse tracheal organ cultures. M. pulmonis multiplied in the tracheal organ cultures, producing inhibition of ciliary activity and histologic tissue damage. The organism grew in close association with the cell membranes but did not appear to attach directly to the membranes or the cilia. Influenza A virus also replicated in tracheal organ cultures, producing ciliary inhibition and more extensive cytopathologic changes. Virus particles were seen by electron microscopy to attach to and cause clumping of the cilia. Simultaneous infection of the organ cultures with mycoplasma and virus resulted in more rapid inactivation of ciliary activity and greater tissue damage than occurred when the cultures were infected with only mycoplasma or virus. Presence of the virus appeared to have no effect on the growth of the mycoplasma; however, the mycoplasma partially interfered with virus replication.

Rheumatoid and nonrheumatoid synovial cell cultures were challenged with Newcastle disease virus and rubella virus in an attempt to confirm reports that rheumatoid synovial cells are relatively resistant to infection with these viruses. Newcastle disease virus caused complete cell destruction by day 7 in both rheumatoid and nonrheumatoid cultures, and peak virus titers were similar. Rubella virus replicated in both rheumatoid and nonrheumatoid synovial cell cultures, and no consistent differences in virus titers were detected. Rubella-infected cell lines were observed for up to 28 days and no virus-specific cytopathic effect was seen.

Carbenicillin is a new semisynthetic penicillin which differs from other penicillins in showing moderate antibacterial activity against Pseudomonas. Its activity in vitro is enhanced at low pH. Serum binding is of low order and does not appreciably alter activity. Strains of Pseudomonas exposed to subinhibitory concentrations of carbenicillin rapidly develop resistance by a mechanism that does not depend upon destruction of the drug. In normal subjects, high levels of anti-Pseudomonas activity are readily obtained in the urine after intramuscular injection. Levels of carbenicillin adequate to inhibit many strains of Pseudomonas can be achieved in serum only with an intravenous administration of a large dose. Carbenicillin appears to exhibit the same low degree of toxicity as do other penicillins.

The in vitro antimicrobial activity of tobramycin and gentamicin was compared against 362 bacterial isolates. The minimal inhibitory concentration (MIC) of tobramycin was fourfold less than the MIC of gentamicin against most of 119 Pseudomonas organisms. Gentamicin and tobramycin had similar in vitro activity against Enterobacteriaceae and Staphylococcus aureus. Proteus rettgeri were commonly resistant to both tobramycin and gentamicin. The 10-mug tobramycin disc separated resistant (MIC >/=5 mug/ml) and susceptible (MIC <5 mug/ml) organisms in 359 of 362 tested. In disc diffusion testing, the tobramycin and gentamicin zone diameters were found to vary significantly with concentrations of magnesium ions in the media employed. The MIC of tobramycin varied with the size of the inoculum, and tobramycin was most effective at a neutral pH.