Although European researchers generally state that few toxic reactions, if any, result from administration of P.A.S., and that it should be given in greater dosage than 15 gm. daily, our experience has been different. In this study 64.3 per cent of the patients had evidence of some degree of toxicity. Fifteen grams per day has been more than our patients, except for a very few, could tolerate when given as the free acid. There was fairly god tolerance on a schedule of 9.6 to 10.5 grams per day and this dosage was found to be therapeutically effective. On the other hand 22 cases (52.4 per cent) showed symptomatic benefit. Of the remainder who exhibited no symptomatic improvement 11.9 per cent were asymptomatic before P.A.S. was given. Perhaps the greatest difference in the drug as we employed it and as used in Europe is that ours was the uncoated tablet of the free acid whereas in Great Britain and on the Continent the investigators used the sodium salt solution or enteric coated tablets of the acid. We wish to stress that in this series P.A.S. was given a most severe test. Eighty-eight per cent of the patients were streptomycin failures. Ninety per cent had bilateral disease. Cavities varied in size from less than 2 cms. to 15 cms. in diameter. Cavitation was present in all cases except six. Of the 40 patients with pulmonary tuberculosis 42.5 per cent had mixed or productive disease, and definite clinical and x-ray improvement directly attributable to P.A.S. was seen in 27 or 67.5 per cent. We also wish to emphasize the apparently great value of P.A.S. in endobronchial tuberculosis. Five patients with pulmonary disease also had endobronchial tuberculosis previously treated unsuccessfully with streptomycin; the lesions healed in all five of these cases. Two patients with tuberculous meningitis suffered a relapse subsequent to six months of streptomycin therapy. Reinstitution of treatment with streptomycin appeared to be ineffective. With the addition of P.A.S. both had remission of their symptoms. The drugs have been discontinued for three months in one of these patients. The spinal fluid chemistry now approaches normal limits. All other patients with tuberculous meningitis who responded favorably but later relapsed, died when streptomycin alone was used. Dunner has stated that resistance to P.A.S. develops in the tubercie bacillus. At least clinically we have evidence to uphold this conclusion. In some cases, after approximately four months of treatment with P.A.S., loss of its effect has been observed, as evidenced by increase of disease. It is highly questionable, therefore, whether one should seek to obtain the combined effect of streptomycin and P.A.S. routinely unless the two drugs are used for a short course, perhaps no longer than three months. It is desirable to have one drug in reserve in the event resistance develops to the other. When a patient is being prepared for surgery P.A.S. might be used preoperatively for two or three months. During surgery and postoperatively, especially in cases of resection, streptomycin alone, or P.A.S. combined with streptomycin, might be used advantageously for one or two months to obviate or control postoperative spreads. In a number of patients it has been observed that the early good effect of P.A.S. was lost after approximately four months. Therefore, when collapse therapy is necessary in a patient receiving P.A.S. it should be instituted as early as the criteria for collapse therapy will permit, before loss of P.A.S. effect may develop.
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Sep 1, 1970
Matthew L Dow + 1
Open Access
