Microbial persistence is the term used to signify the phenomenon whereby microbes that are susceptible to a drug in vitro can nevertheless survive long continued exposure to it in vivo (1, 2).An unusual form of microbial persistence displayed by tubercle bacilli of human origin was described in previous reports from this laboratory (3-5). Relatively large populations of bacilli (one to three million cells) could be made to "vanish" uniformly from the tissues of mice that had received two compounds; the nicotinamide derivative pyrazinamide, and isoniazid, in appropriate time-dose relationships. The criteria for "vanishing" were failure to detect any bacilli by; microscopy, culture, or guinea pig inoculation of the tissues of the infected mice. The "vanishing" did not mean that the bacilli were totally eliminated from the tissues. On the contrary, after a 90 day treatment-free interval, culturable tubercle bacilli could be demonstrated in approximately one-third of the animals. The question immediately arose whether all of the tubercle bacilli had been eradicated in the other two-thirds of the animals in each experiment, or whether the bacilli were still present in them but were in a iatent state.By latent is meant a phase during which the infection is hidden beyond all diagnostic reach. In such a phase, the bacilli conceivably could be present in some altered form or they could be unaltered, but so few in number tl~t they escape detection. In view of the demonstrated sensitivity of the culture techniques employed, it seemed clear that at the most only a very few ~naltered bacilli could be present and escape detection. It was noted (4), however, that if a microbial alteration took the form of sterilization without death, fairly large populations, being nonculturable, might vanish from the tissues because of the insensitivity of microscopy as a detection technique. In the studies reported (3), acid-fast bacilli could not be found with any regularity on microscopy of tissue sections when the organ census was below I × 105 per ml and only

Populations of tubercle bacilli of human origin exposed in vivo to pyrazinamide and a companion drug, vanished from the tissues of the mouse in so far as could be determined by microscopy, culture, or guinea pig subinoculation. The vanishing did not represent a complete elimination of the tubercle bacilli from all the animals. 90 days after the completion of treatment, tubercle bacilli could be cultured from approximately one-third of the animals examined at that time. This complete disappearance of the tubercle bacilli thus meets the definition of a truly latent infection in that the infection is present but is hidden beyond the limits of diagnostic reach. All but one of the strains of tubercle bacilli which survived in the animals and were detectable in the posttreatment period, were susceptible to pyrazinamide when tested under appropriate conditions in vitro. Only two factors could be identified which were essential for the uniform occurrence of the disappearance of tubercle bacilli: the administration of the pyrazinamide in a high daily dosage for at least eight of a total of 12 weeks of antimicrobial therapy; and the concurrent or prior exposure of the microbial populations to isoniazid or in some cases to other antituberculous drugs. The observations suggest that the ability of pyrazinamide-containing chemotherapies to bring about the disappearance of a tubercle bacillus is closely related to the occurrence of some alteration in the bacillus, essential for maximal pyrazinamide action, in response to environmental influences, including other antituberculous drugs present in the environment.

In the preceding paper (1) evidence was presented that the phenomenon whereby large populations of tubercle bacilli can be made to "disappear" from the tissues of mice is produced by an alteration of the bacilli to a sterile ~ state. I t was further shown: that the phenomenon is a specific one produced by the actions of two drugs, pyrazinamide and isoniazid; that it occurs in all or virtually all of the animals in an experimental group; and that once assumed, the sterile state endures for a period measurable in months. Whether the sterile bacilli are morphologically altered cannot be stated from the available evidence. The only indication of a host influence in maintaining the microbial sterility is the increased incidence of microbial revival when large daily doses of cortisone are given in the 3rd or 4th month after sterilization. The present paper is concerned with observations that serve to characterize more sharply this phenomenon of the sterilization of tubercle bacilli in vivo.

Aims: To examine the safety implications of omitting first day clinical review following phacoemulsification cataract surgery. Methods: 362 patients were randomly assigned to ''same day discharge'' (SDD) or ''next day review'' (NDR). All patients were reviewed approximately 2 weeks after surgery. Results: Of the 174 patients randomised to NDR, 14 (8.0%) were treated for raised intraocular pressure (25-48 mm Hg) on the first postoperative day. Four received increased topical steroids for uveitis (two) and corneal oedema (two). One patient was treated for a significant wound leak. 12 (6.9%) required additional reviews before 2 week follow up for treatment of the following complications: drop toxicity (six), raised intraocular pressure (five), and corneal abrasion (one). Of the 188 randomised to SDD, six (3.2%) returned to the department before the planned review for reassurance of patients' concerns regarding eye symptoms (three), drop toxicity (one) and follow up of previously raised intraocular pressure (one). There were two cases of iris prolapse in the SDD group. In one case, the complication was anticipated and early review had been arranged. Postoperative acuities of 6/12 or better were achieved in 83% of both SDD and NDR patients (p = 0.96 by x 2 test). Postoperative quality of life scores at 4 months indicating ''no or hardly any concern about vision'' (VCM1 questionnaire index ,1.0) were achieved in 67% SDD and 72.5% NDR (p = 0.26). Conclusion: The intention to discharge patients on the day of surgery, with planned postoperative review at 2 weeks, was associated with a low frequency of serious ocular complications. Differences in the proportions achieving a good visual outcome between the two groups, based on 2 week visual acuity and 4 month quality of life, were not significant.