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Oropharyngeal histoplasmosis treated with diamidinodiphenylamine
290
CORRESPONDENCE OROPHARYNGEAL HISTOPLASMOSIS TREATED WITH DIAMIDINODIPHENYLAMINE
SIR,--On 1st September, 1957, a male patient of 46 years of age entered the hospital. H e h a d ulcerous, g r a n u l o m a t o u s a n d v e g e t a t i n g lesions in the m u c o s a of t h e left h a l f of t h e palate, g u m s , lower lips, tonsils, o r o p h a r y n x , n a s o p h a r y n x a n d r i g h t nostril. T h e vocal cords were oedem a t o u s a n d congested. T h e m a i n c o m p l a i n t s of the p a t i e n t were pain o n swallowing, weakness, considerable loss of w e i g h t a n d c o u g h d u r i n g t h e last 2 or 3 m o n t h s . T h e spleen was m o d e r a t e l y enlarged. T h e t e m p e r a t u r e oscillated b e t w e e n 37 ° and 38°C. E x u d a t i v e lesions were o b s e r v e d i n t h e lungs. T y p i c a l e l e m e n t s of t h e f u n g u s Histoplasma capsulaturn were f o u n d in s m e a r s a n d in a biopsy. C u l t u r e s of t h e same o r g a n i s m were o b t a i n e d o n S a b o u r a u d glucose agar w i t h penicillin a n d s t r e p t o m y c i n . W e t h o u g h t t h a t this was a severe case of evolutive histoplasmosis a n d t h a t a specific t r e a t m e n t was necessary.
It has been shown by Mackinnon, Artagaveytia-Allende and Garcia-Zorrdn (1958) that the growth of H. capsulatum is inhibited by the addition to the culture medium of diamidinodiphenylamine dihydrochloride (M. & B. 938) in concentrations of between 2 and 10[zg. per c.c. The strain isolated from our patient was inhibited by 2 to 5 ~zg. per c.c. The in vitro sensitivity of H. capsulatum is similar to that of Paracoccidioides brasiliensis, the causal organism of South American blastomycosis, and to that of Coccidioides immitis. The drug has been efficient in a case of South American blastomycosis (Transactions (1957), 51, 371) and interesting results were obtained in the experimental coccidioidomycosis of the mouse (Transactions (1958), 52, 92). Progressive doses of 25, 75, and 100 rag. of the drug were administered intravenously to test the sensitivity of the patient. Afterwards the following doses were injected daily : 150, 150, 250, 250, 250, 150, 150 and 150 mg. Isoniazid and streptomycin were also administered. After a rest period of 22 days a new course of 10 injections of 250 mg. was given. An antihistamine, Benadryl or Fenergan, was given before the diamidine but the fall in the blood pressure and the headaches were not prevented. The higher doses produced vomiting. At the end of the first series we noticed a remarkable improvement of the oropharyngeal lesions and after the rest period the recovery was almost complete. After the second series and after removal of remnants of some carious teeth the recovery was complete. The lesions of the lungs improved. The patient, a farmer, recovered his normal body weight and returned to his hard work. We did not observe relapses during the 31 months after the end of the treatment. We are, etc., JUAN E. MACKINNON VOLKER STAPFF
Instituto de Higiene Facultad de Medicina Montevideo-Uruguay. 6th March, 1958. REFERENCE : MACKINNON,J. E., ARTAGAVEYTIA-ALLENDE,R. C. & GARCIA-ZoRRdN,N. (1958). Rev. Latinoamericana de Microbiologia., 1, in press.
TRIALS OF NEW TRYPANOSOMICIDAL DRUGS
Sm,--Dr. Baker recently expressed the opinion (Transactions, 51, 467) that it would be unwise to commence clinical trials on new trypanosomicidal drugs which had been tested
CORRESPONDENCE OROPHARYNGEAL HISTOPLASMOSIS TREATED WITH DIAMIDINODIPHENYLAMINE
SIR,--On 1st September, 1957, a male patient of 46 years of age entered the hospital. H e h a d ulcerous, g r a n u l o m a t o u s a n d v e g e t a t i n g lesions in the m u c o s a of t h e left h a l f of t h e palate, g u m s , lower lips, tonsils, o r o p h a r y n x , n a s o p h a r y n x a n d r i g h t nostril. T h e vocal cords were oedem a t o u s a n d congested. T h e m a i n c o m p l a i n t s of the p a t i e n t were pain o n swallowing, weakness, considerable loss of w e i g h t a n d c o u g h d u r i n g t h e last 2 or 3 m o n t h s . T h e spleen was m o d e r a t e l y enlarged. T h e t e m p e r a t u r e oscillated b e t w e e n 37 ° and 38°C. E x u d a t i v e lesions were o b s e r v e d i n t h e lungs. T y p i c a l e l e m e n t s of t h e f u n g u s Histoplasma capsulaturn were f o u n d in s m e a r s a n d in a biopsy. C u l t u r e s of t h e same o r g a n i s m were o b t a i n e d o n S a b o u r a u d glucose agar w i t h penicillin a n d s t r e p t o m y c i n . W e t h o u g h t t h a t this was a severe case of evolutive histoplasmosis a n d t h a t a specific t r e a t m e n t was necessary.
It has been shown by Mackinnon, Artagaveytia-Allende and Garcia-Zorrdn (1958) that the growth of H. capsulatum is inhibited by the addition to the culture medium of diamidinodiphenylamine dihydrochloride (M. & B. 938) in concentrations of between 2 and 10[zg. per c.c. The strain isolated from our patient was inhibited by 2 to 5 ~zg. per c.c. The in vitro sensitivity of H. capsulatum is similar to that of Paracoccidioides brasiliensis, the causal organism of South American blastomycosis, and to that of Coccidioides immitis. The drug has been efficient in a case of South American blastomycosis (Transactions (1957), 51, 371) and interesting results were obtained in the experimental coccidioidomycosis of the mouse (Transactions (1958), 52, 92). Progressive doses of 25, 75, and 100 rag. of the drug were administered intravenously to test the sensitivity of the patient. Afterwards the following doses were injected daily : 150, 150, 250, 250, 250, 150, 150 and 150 mg. Isoniazid and streptomycin were also administered. After a rest period of 22 days a new course of 10 injections of 250 mg. was given. An antihistamine, Benadryl or Fenergan, was given before the diamidine but the fall in the blood pressure and the headaches were not prevented. The higher doses produced vomiting. At the end of the first series we noticed a remarkable improvement of the oropharyngeal lesions and after the rest period the recovery was almost complete. After the second series and after removal of remnants of some carious teeth the recovery was complete. The lesions of the lungs improved. The patient, a farmer, recovered his normal body weight and returned to his hard work. We did not observe relapses during the 31 months after the end of the treatment. We are, etc., JUAN E. MACKINNON VOLKER STAPFF
Instituto de Higiene Facultad de Medicina Montevideo-Uruguay. 6th March, 1958. REFERENCE : MACKINNON,J. E., ARTAGAVEYTIA-ALLENDE,R. C. & GARCIA-ZoRRdN,N. (1958). Rev. Latinoamericana de Microbiologia., 1, in press.
TRIALS OF NEW TRYPANOSOMICIDAL DRUGS
Sm,--Dr. Baker recently expressed the opinion (Transactions, 51, 467) that it would be unwise to commence clinical trials on new trypanosomicidal drugs which had been tested