Edith M. Lincoln

Initial tuberculous infectiondue to drug-resistant organisms

Summary A survey of pretreatment cultures in 2,500 children with primary tuberculosis from 7 pediatric chest clinics in the United States has revealed that, since the beginning of chemotherapy for tuberculosis, 7 children have been found to be infected initially with isoniazid-resistant tubercle bacilli and 11 children have been found to be infected initially with streptomycin-resistant organisms. The literature on tuberculous infection caused by isoniazid-resistant organisms is reviewed. The significance of such infections and the implications of these findings for future diagnostic and therapeutic management of tuberculosis are discussed.

Tuberculin reactions in children

Summary 1. In a study of 1,264 measured tuberculin reactions, no positive correlations could be found between the size and intensity of the reactions and the location of tuberculous disease, the size or activity of the lesion, or the prognosis. 2. The reaction to the intracutaneous tuberculin test tends to vary in size and intensity directly with the size of the dose and with the age of the child. 3. There is no sex variation in the size and intensity of the reaction when age and dosage are constant. 4. The initial test should not be more than 0.01 mg. and a negativetest should mean negative to 1 mg. 5. Definite criteria as to size of reaction and time of reading must beadhered to if false reactions are to be eliminated. 6. Tuberculin dilutions up to 1:10,000 are relatively stable, and dilutionsneed not be made more often than once a month. 7. Syringes and needles should be used for tuberculin testing only and separate ones kept for the various dilutions. 8. A positive tuberculin reaction is unlikely to become negative withinthe span of childhood, and this is even less likely to occur in cases in which there has been a diagnosis of clinical tuberculosis than in cases in which the positive test has been the only manifestation of tuberculosis. 9. It is usually unnecessary and undesirable to repeat a tuberculintest during childhood if a tuberculin test has once been positive, as the test only rarely becomes negative during these years. 10. There has been a marked decrease in the number of infants infected with tuberculosis in the series studied on the Childrens Medical Service of Bellevue Hospital in the past seven years as compared with a similar preceding period.

Observations on the effect of induced hyperglycemiaon the glucose content of the cerebrospinal fluid in patients with hydrocephalus

Summary Tests of the diffusion of glucose from the blood into the cerebrospinal fluid have been performed in thirteen children with normal ventricles and ten children with hydrocephalus. In the former group the glucose content of the cerebrospinal fluid increased by 30 mg. per 100 c.c. or more. In the hydrocephalic children the increase in glucose content of the ventricular fluid was always below the figure established as normal. This was true of the lumbar region also, whenever the hydrocephalus was not associated with a spinal block due to tuberculous meningitis or with active meningitis.

Subacute pneumonia in children

Summary A subacute form of pneumonia has been described which cannot be classified on a pathologic basis since all our typical cases recovered. It is frequently associated with infections of the upper respiratory tract and has a subacute or prolonged course. Because of its possible tendency to cause permanent damage to the lung, the disease should be treated, even when mild. The upper respiratory infection must not be neglected, and postural drainage of the lung should invariably be used, together with bronchoscopy in severe cases or when collapse of a lobe occurs. Cases which have not cleared completely on roentgenologic examination or by physical signs should have a bronchogram before a diagnosis of bronchiectasis is excluded.

Chemotherapy of tuberculosis in children.

Streptomycin is the most effective tuberculostatic agent. It is unsuitable for prolonged therapy because of its potential toxicity, especially for the vestibular branch of the VIII C nerve, and because of the tendency of the tubercle bacillus to become resistant after relatively short periods of treatment. Experience only will prove ultimately which lesions respond best to streptomycin therapy. Because of its limitations its use as a sole chemotherapeutic agent should be restricted to cases which can be benefited or cured by short courses of therapy not exceeding six weeks. It is of great value in controlling tuberculosis for short periods of time so as to permit surgical procedures and collapse therapy. Streptomycin is contraindicated in forms of tuberculosis such as primary infections and minimal chronic pulmonary tuberculosis which usually respond without chemotherapy. It should not be used in an attempt to prevent complications; meningitis and other less serious complications may develop during treatment. Promizole® was found to be ineffective in the treatment of tuberculous meningitis; five out of seven cases of acute generalized miliary tuberculosis treated with promizole® have survived 2½ to almost five years and are free from miliary tuberculosis. Combined therapy with streptomycin and promizole® was undertaken in order to utilize the advantages of the rapid action of streptomycin with the prolonged bacteriostatic action of the sulfone which can be given safely and effectively for a period of years. By combining the two drugs it was hoped to delay the emergence of resistant organisms and to secure an enhanced effect from both streptomycin and promizole®. Ten children with miliary tuberculosis have been treated by combined therapy. One patient died after six days of treatment and another of a relapse from meningitis 11 months after the initial diagnosis of miliary tuberculosis. No relapse of miliary tuberculosis has occurred in patients treated with promizole® whether or not it was combined with streptomycin. Eighteen cases of tuberculous meningitis have been treated with streptomycin by the intramuscular and intrathecal routes and with promizole® orally. Thirteen cases survived from 5 to 23 months. There have been no severe neurologic sequelae. All the survivors are apparently normal mentally.