Two combinations of drugs were compared in a cooperative study of 32 children with acute hematogenous miliary tuberculosis treated at seven different pediatric centers under a common protocol. Eighteen children were given intramuscular streptomycin with oral para-aminosalicylic acid and promizole?; 14 children were given streptomycin and para-aminosalicylic acid without promizole?. A one year follow-up of this small group showed no significant differences in the results due to the use of promizole?. However, 5 of 10 children treated initially with a streptomycin dose of 20 mg./kg. intramuscularly twice a day were either dead or had developed meningitis, while only 2 of 22 children treated with a 50 mg. dose died, one of these having developed meningitis.Twenty-six of the original 32 patients were alive 12 months after the start of treatment. Relapse of miliary disease was not encountered during the first year of this study.The optimum duration of treatment is still uncertain. The combination of para-aminosalicylic acid with streptomycin may be assumed to delay the emergence of streptomycin-resistant organisms in miliary and meningeal diseases just as it does in pulmonary tuberculosis. Thus, a six month or even one year course of streptomycin can now be considered feasible. Although some patients may have been treated longer than necessary, the observation that three patients developed meningitis at 110, 125 and 130 days of study suggests that treatment should be relatively long. A child who survives miliary tuberculosis only to develop tuberculous meningitis has received little real benefit from therapy. As the over-all mortality in miliary tuberculosis is lowered, the prevention of meningitis in the survivors becomes an increasingly important goal.Disturbing side effects of promizole? therapy were less frequent among the patients reported here than among other reported groups. The daily dose, however, was small in comparison with the amounts recommended by Lincoln.Ninety-three children with tuberculous meningitis, 23 of whom also had miliary tuberculosis, were observed for a period of one year while under treatment with a combination of tuberculostatic agents. Half the patients were given intramuscular streptomycin, intrathecal streptomycin, and para-aminosalicylic acid and promizole? by mouth. The remainder received an identical regimen except that promizole? was omitted.Forty-two patients (45%) survived the first year; 24 of these had no serious sequelae from the disease. No differences were noted in the course of the disease among those who received promizole? and those who did not, and the one year survival rates in the two groups were practically identical.Revision of the streptomycin dosage, which took place after the study had been in progress seven months, produced results which appear to justify the change. An intramuscular streptomycin dose of 50 mg./kg. twice daily to a maximum of 1.5 gm. twice daily was apparently more effective than 20 mg./kg. twice daily.Lincoln whose results in childhood meningitis are the most successful yet reported and the British Medical Research Council both depend on a regimen which includes intrathecal streptomycin. The investigators in this study favor its use and had no unusual difficulty with it.Relapse occurred in eight children, all of whom survived the first year.A poorer prognosis was noted in infants, in nonwhites, and in patients with miliary tuberculosis.The most common toxic effects were due to streptomycin, which caused vestibular damage in a large number of patients, but the capacity of children to compensate for this dysfunction is so great that this risk is minor in the face of the otherwise hopeless outcome. Streptomycin may have been partially responsible for marked hearing loss in six.Para-aminosalicylic acid and promizole? act less rapidly than streptomycin. They are easily administered and rarely produce significant toxicity even when given over extended periods. They appear to reinforce the effect of streptomycin, and para-aminosalicylic acid at least postpones the emergence of streptomycin resistance. Their use appears to decrease the likelihood of relapse. Finally, their daily use at home maintains the patient's awareness that he requires prolonged medical supervision and brings him back for examination when his drug supply needs replenishing. The use of these drugs with streptomycin in tuberculous meningitis is recommended.
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机译：在一项共同研究方案下，在七个不同的儿科中心接受治疗的32例急性血源性粟粒性肺结核儿童的合作研究中，比较了两种药物的组合。 18名儿童接受了肌内链霉素，口服对氨基水杨酸和普罗米唑治疗; 14名儿童接受了链霉素和对乙酰氨基水杨酸，但未注射普罗米唑。对这一小组进行的为期一年的随访结果显示，由于使用了普罗米唑，结果无显着差异。但是，最初使用链霉素剂量为20 mg./kg的10名儿童中有5名接受了治疗。每天两次肌内注射均已死亡或发展为脑膜炎，而22名儿童中只有2名接受了50 mg的治疗。剂量死亡，其中一名已发展为脑膜炎。最初的32名患者中有26名在开始治疗后的12个月内还活着。在这项研究的第一年中未发生粟粒性疾病复发。最佳治疗时间仍不确定。对氨基水杨酸与链霉素的结合可以像在肺结核中一样，在粟粒性和脑膜疾病中延缓抗链霉素生物的出现。因此，现在认为六个月甚至一年的链霉素疗程是可行的。尽管某些患者的治疗时间可能比必要的时间长，但观察到三名患者在研究的110、125和130天出现脑膜炎，提示治疗应该相对较长。幸存于粟粒性肺结核而仅发展为结核性脑膜炎的儿童几乎没有从治疗中获得任何实际好处。随着粟粒性结核病总体死亡率的降低，预防幸存者中的脑膜炎已成为一个越来越重要的目标。在此报告的患者中，接受治疗的频率低于其他报告的人群。然而，与林肯建议的每日剂量相比，每日剂量很小。观察到93例结核性脑膜炎患儿（其中23例也患有粟粒性结核病）在接受抗结核药联合治疗的情况下观察了一年的时间。一半的患者接受了肌内链霉素，鞘内链霉素，对氨基水杨酸和丙咪唑？用嘴。其余的人接受了相同的疗程，除了那个普罗米唑？第一年有42例患者（45％）存活。其中24例没有因该疾病引起的严重后遗症。在服用丙咪唑的人中，病程中没有发现差异吗？两组之间的一年生存率几乎相同。研究进行七个月后对链霉素剂量进行了修订，结果似乎证明了这一改变的合理性。肌内链霉素的剂量为50 mg./kg。每天两次，最大1.5克。每天两次显然比20 mg./kg更有效。林肯治疗儿童脑膜炎的结果是迄今为止最成功的报道，英国医学研究理事会（British Medical Research Council）均采用包括鞘内链霉素在内的治疗方案。这项研究的研究者赞成使用它，并且没有异常困难。复发发生在8名儿童中，他们都在第一年存活了下来。婴儿，非白人和粟粒性结核患者的预后较差。链霉素的常见毒性作用是由链霉素引起的，该链霉素在许多患者中引起前庭损害，但是儿童弥补这种功能障碍的能力是如此之大，以致面对原本无望的结果，这种风险很小。链霉素可能是造成六人明显听力下降的部分原因。氨基水杨酸和普罗米唑？作用不如链霉素快。它们很容易服用，即使长期服用也很少产生明显的毒性。它们似乎增强了链霉素的作用，对氨基水杨酸至少推迟了链霉素耐药性的出现。它们的使用似乎降低了复发的可能性。最后，他们在家中的日常使用使患者意识到他需要长时间的医疗监督，并在需要补充药品时将其带回检查。建议将这些药物与链霉素一起用于结核性脑膜炎。
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