- Email: [email protected]
Congenital tuberculosis
166
Tubercle,_Lond., 0 9 5 8 ) , 39, 166
CASE
REPORTS
Congenital Tuberculosis By P I N C H A S W A Y L and O L G A S T E I N From the Chest Department and the Iustitute of Pathol~y, Hadassah University Hospital, Hebrew University-Hadassah Medical School, Jerusalem T h e p r o b a b l e i n t r a - u t e r i n e t r a n s m i s s i o n o f m a t e r n a l t u b e r c u l o s i s to t h e d e v e l o p i n g foetus h a s so far b e e n r e p o r t e d in I 4 4 cases. O n e h u n d r e d a n d t h i r t y - t h r e e w e r e i n c l u d e d in a c r i t i c a l r e v i e w b y C o r n e r a n d B r o w n in x955 a n d I I h a v e b e e n p u b l i s h e d since t h e n ( L e l o n g a n d others, 1954; R a d e m a c h e r , I 9 5 5 ; B r e t o n a n d D u b o i s , 1955; R a v i n a a n d D a u n a y , 1955; O r m o s a n d Pzildy, i 9 5 5 ; R i o r d a n , i 9 5 5 ; D u b s k y , 1955; H u d s o n , 1956; R o m a g n y a n d others, 1956 ). T h i s r e n e w e d i n t e r e s t in t h e p r o b l e m a p p e a r s j u s t i f i e d in v i e w o f t h e f a c t t h a t m a n y i n v e s t i g a t o r s - a s l a t e as 1948 ( D e b r e a n d o t h e r s ) - h a v e questioned the e x i s t e n c e o f f o e t a l i n f e c t i o n d u r i n g i n t r a - u t e r l n e life. T h e p r e s e n t a r t i c l e deals w i t h 3 m o r e cases in w h i c h t h e p r e s e n c e o f c o n g e n i t a l t u b e r c u l o s i s has b e e n p r o v e d in y o u n g infants o n c l i n i c a l a n d p a t h o l o g i c a l examinations.
Case Reports Case l A 3-week-old female child was admitted to the children's ward of the Hadas;ah-University Hospital, for severe respiratory distress and cyanosis. Both parents and their 2o-months-old first child, were healthy. A paternal aunt had been found to have pulmonary tuberculosis three 3"ears before, but her disease was clinically arrested and the sputum negative before the birth of the present child. The delivery of the patient was normal following an uneventful pregnancy. The weight at birth was ~,76o g. and the breast-fed child gained weight during the next two weeks. Five days prior to admission the child developed a cold and refused food. During the next few days progressive respirator)' distress developed until admission. On admission the pertinent findings were severe respiratory distress and cyanosis. Moist rfiles were heard all over both lungs. The child was put in art oxygen tent and given antibiotics. During the subsequent three days the temperature ranged up to 39°C. (lo~ ° F.) and there was no change in the respiratory status. X-ray examination revealed an intense mottling of both lungs. The child dled on the fourth day after admission, at the age of 4 weeks, with a diagnosis of bilateral pneumonia. .tVecrol,sy Findings.- The body was that of a female child x~cighlng ~,85o g. The essential gross findings were confined to the lungs. The pleural surface of the lungs was studded with greyish-wlfite. nodules measuring x-8 ram. in diameter. The consistency of the remaining lung tissue was increased. On cut surface the nodules were scattered throughout both lungs, leaving only a small amount of intact lung tissue. Some of the nodules were softer and on pressure oozed ~ome light-yellowish material. A similar material was contained within the main bronchi and trachea. The hilar and carinal lymph nodes were slightly enlarged. The spleen and liver were congested. Histological Exambzation.- The greyish nodules in the lungs were composed of an amphophilic material surrounded by an inflammatory cellular cxudate. In some sections the lesions were bronehopneumonie in form, the bronchioles and the surrounding alveoli being filled with granulocytes and mononuelear cells. No typical tubercles or giant cells were found, but all the lesions in the lungs swarmed with acid-fast bacilli. In a few alveoli signs of amniotic fluid aspiration were found, indicated by the presence of cornified material, presumably originating from the foetal epidermis. The tfilar and carinal lymph nodes were the gite of caseous necrosis and round cell and granulocytic infiltration. In the liver and spleen a few loci of necrosis and an occasional giant cell were found. In all the necrotic loci acid-fast bacilli were demonstrated. Subsequent Maternal History.-After tuberculosis was revealed at the child's post-mortem the mother was re-examined. On repeated endometrial biopsies by histological and bacteriological
CONGENITAL "TUBERCULOSIS
167
examinations, tuberculous endometritis was found. She was treated with streptomycin and PAS for the next eight months, until culture and histological examination of the endometrium gave normal results. Repeated x-ray studies of the chest and cultures of the sputum were always negative. Cases 2 and 3
A 36-year-old woman, known to be suffering from widespread tuberculosis, gave birth to twins in tile seventh month of pregnancy. The babies were separated from the mother immediately after birth and placed in incubators. The infants weighed 1,8oo g. each. Bah)" A died at the age of 23 days without clinical evidence of illness. Baby B had a bout of fever and on x-ray examination there was diffuse mottling of both lungs. It died at the age of 33 days. The mother died shortly after delivery and generalized tuberculosis of lungs, abdominal and pelvic organs was found at necropsy. Baby A (Case 2 ) . - The necropsy findings of Baby A were chiefly confined to the lungs. Both lungs were studded with tiny grey nodules. Histological examination of the lungs revealed that the nodules were composed of caseous material surrounded by round-cell infiltration, but no giant cells. Tim lesions were situated intra-alveolarly and in alveolar walls and only occasionally were bronclfioles involved. All the lesions contained numerous acld-fast bacilli and phagocytosed acidfast granules. The hilar lymph nodes showed caseating loci and epithefioid tubercles. In the liver several small foci of granulomatous infiltration were found. Baby B (Case 3 ) - - I n Baby B widespread tuberculous involvement of lungs, liver, spleen and lxmph nodes was found. These organs were studded with grey nodules x-2 ram. in diameter. In the lungs tllere were some areas wilere the nodules were confluent. Histologically, the findings in the lungs were similar to those of Baby"A. In addition, typical tubercles with giant ceils were found and there was invoh'ement of bronchial walls; some tubercles were seen in the intima of veins. The hilar and mesenteric 1)wnph nodes were the site of easeating tubercles. The entire liver parenchyma was studded with tubercles showing caseation necrosis. Acid-fast bacilli were found in all these lesions. In the kidneys tubercles with giant cells were seen. In the brain and meninges there were loci of round cell and leucocytic infiltration.
Comment I n a recent review, C o r n e r a n d Brown (I955) re-stated the criteria of Beitzke (I935) for the diagnosis of congenital tuberculosis: T h e lesion in the child m u s t be proved to be tuberculous. E x t r a - u t e r i n e infection m u s t be excluded b y d e m o n s t r a t i n g e i t h e r (a) the presence of tuberculous lesions at birth, or (b) a p r i m a r y complex in the liver a n d regional nodes, or (c) the child m u s t have been i m m e d i a t e l y separated from the m o t h e r a n d other possible sources o f infection. All 3 c h i l d r e n a n d both mothers presented here h a d proved tuberculous lesions o n histological a n d bacteriological study. Cases 2 a n d 3, the twins, were separated from the m o t h e r i m m e d i a t e l y after birth. A l t h o u g h the first infant h a d not been removed from the m o t h e r i m m e d i a t e l y after birth, we believe t h a t extra-uterine infection can be excluded because: (x) th~ d e v e l o p m e n t of such extensive p u l m o n a r y lesions w o u l d require a longer period t h a n the four weeks of post-natal life (Reichle a n d Wheelock, i939). (2) Tuberculosis in the m o t h e r was proven to be confined to the genital organs, thus e l i m i n a t i n g the possibility of post-natal infection (Hertzog a n d others, i949). T h r e e possible routes of i n t r a - u t e r i n e transmission of tuberculous infection have been suggested in previous publications. I n b l o o d - b o r n e infections the bacilli pass t h r o u g h the p l a c e n t a into the u m b i l i c a l vein, a n d a p r i m a r y complex is formed i n the foetal liver a n d portal l y m p h nodes. Sometimes, the b l o o d - b o r n e bacilli m a y by-pass the liver t h r o u g h the ductus venosus, a n d a p r i m a r y complex m a y form in the lungs. T h e other routes involve either swallowing or aspirating infected a m n i o t i c fluid. I n the first instance, p r i m a r y intestinal tuberculosis would develop, a n d in the latter a widespread p u l m o n a r y infection would result. I n the latter case the lesion would be confined to the lungs, b u t later i n v o l v e m e n t of hilar l y m p h nodes a n d even a h a e m a t o g e n o u s spread m i g h t occur (Horley, i95~ ). We presume that the route of infection in our first case was most p r o b a b l y b y aspiration of a m n i o t i c fluid. T h e severest lesions were found i n the lungs a n d there
I68
TUBERCLE
was a b r o n c h o p n e u m o n i c s p r e a d ; k e r a t i n scales p r o b a b l y o r i g i n a t i n g from the a m n i o t i c fluid w e r e p r e s e n t w i t h i n the e x u d a t e . I n a d d i t i o n , t h e r e was a s e c o n d a r y tuberculous s p r e a d to h i l a r l y m p h nodes a n d evidence o f h a e m a t o g e n o u s s p r e a d to t h e liver a n d spleen. I n Case 2 ( B a b y A ) , t h e findings w e r e s o m e w h a t s i m i l a r to those o f Case I a n d suggested a s p i r a t i o n as t h e r o u t e o f infection. T h e lack o f a p r i m a r y c o m p l e x in the liver or lungs w o u l d speak against t b e h a e m a t o g e n o u s route o f infection. T h e absence o f gastro-intestinal lesions e x c l u d e d swallowing o f a m n i o t i e fluid as the r o u t e of infection. I n the t h i r d case ( B a b y B), the i n v o l v e m e n t was so w i d e s p r e a d a n d b o t h ' e a r l y a n d late changes were seen in all the organs, t h a t no conclusions as to t h e r o u t e o f infection could b e d r a w n . T h e final d i s s e m i n a t i o n was b y the blood s t r e a m a n d tubercles could b e shown in t h e i n t i m a o f p u l m o n a r y veins. I t has b e e n n o t e d b y some investigators that, even i f tuberculous lesions are f o u n d in" tile p l a c e n t a , n o t all the c h i l d r e n b o r n o f tuberculous m o t h e r s d o b e c o m e infected in utero ( C a l m e t t e , cited b y R i c h , x95i ). T h i s has b e e n a t t r i b u t e d to resistance o f the foetus d u e to t h e low o x y g e n tension o f t h e foetal blood (Rich, 1951 ; R i c h a n d Follis, 1942; V o n v a l d , i937).
Summary T h r e e cases o f c o n g e n i t a l tuberculosis a r e presented, 2 being in twins. T i l e cases fulfil the c r i t e r i a o f Beitzke for the diagnosis o f c o n g e n i t a l tuberculosis. I n Case i the r o u t e o f the i n t r a - u t e r i n e infection was b y aspiration, in the o t h e r 2 cases either b y a s p i r a t i o n or t h r o u g h the b l o o d s t r e a m . Tile authors wish to thank Dr Hupert from the Beth Meir Hospital and Prof Casper from the Pathological Institute, Beilinson Hospital, for their kind help and permission to publish Cases 2 and 3, and Drs Mendes and Toaf for their kind information concerning Case I. We also wish to acknowledge the helpful interest of Prof Ungar, Head of Dept. of Pathology, Hebrew UniversityHadassah Medical School.
References Beitzke, H. (x935) Ergebn. ges. TuberkForsch., 7, i. Breton, A., and Dubois, O. 0955) Echo mgd. Word.., 26, 233. Comer, B. D., and.Brown, N.J. 0955) Thorax, xo, 99. Debre, R., Furiet-Laforest, - . , and Royer, P. (x948) Arch.fran9. Pgdiat., 5, °55Dubsky, F. 0955) Canad. reed. Ass. J., 73, 66~. Hertzog, A. J., Chapman, S., and Herring, J. 0949) Amer. o7. din. Path., x9, I x39. Horley, J. F. (x952) Arch. Dis. Childh., ~7, x67. Hudson, F. P. 0956) Arch. Dis. Childh., 3t, 136. Lelong, M. R., Rnssler, A., Laumonier, R., and Roussel, A. (x954) Arch. Anat. apth., 3o, t86. Ormos, J., and P~ldy, L. 0955) 22bl. allg. Path. path. Anat., 94, xx7. Ra}temacher, M. 0955) Kinderiirztl. Prax., ~3, ~98Ravina, J., and Daunay, J . J . (i 955) Bull. F/d. Gyn/c. Obstet.franf., 7, 41 x. Reichle, H. S., and Wheelock, M. C. 0939) Arch. Path., 28, 799Rich, A. R. (I951) The Pathogenesls of Tuberculosis, ~nd edition, Blackwell Scientific Publications, Oxford. Rich, A. R., and Follis, R. H., Jr. (x94a) JohnsHopk. Hosp. Bull., 7 x, 345. Riordan, T. P. 0955) N.Z. reed. J., 54, 568. Romagny, G., Fontvielle, J., and Esclangon, - . 0956) Pediatric, xx, 594. Vorwald, A.J. 0937) Amer. Rev. Tuberc., 35, 26o.
Tubercle,_Lond., 0 9 5 8 ) , 39, 166
CASE
REPORTS
Congenital Tuberculosis By P I N C H A S W A Y L and O L G A S T E I N From the Chest Department and the Iustitute of Pathol~y, Hadassah University Hospital, Hebrew University-Hadassah Medical School, Jerusalem T h e p r o b a b l e i n t r a - u t e r i n e t r a n s m i s s i o n o f m a t e r n a l t u b e r c u l o s i s to t h e d e v e l o p i n g foetus h a s so far b e e n r e p o r t e d in I 4 4 cases. O n e h u n d r e d a n d t h i r t y - t h r e e w e r e i n c l u d e d in a c r i t i c a l r e v i e w b y C o r n e r a n d B r o w n in x955 a n d I I h a v e b e e n p u b l i s h e d since t h e n ( L e l o n g a n d others, 1954; R a d e m a c h e r , I 9 5 5 ; B r e t o n a n d D u b o i s , 1955; R a v i n a a n d D a u n a y , 1955; O r m o s a n d Pzildy, i 9 5 5 ; R i o r d a n , i 9 5 5 ; D u b s k y , 1955; H u d s o n , 1956; R o m a g n y a n d others, 1956 ). T h i s r e n e w e d i n t e r e s t in t h e p r o b l e m a p p e a r s j u s t i f i e d in v i e w o f t h e f a c t t h a t m a n y i n v e s t i g a t o r s - a s l a t e as 1948 ( D e b r e a n d o t h e r s ) - h a v e questioned the e x i s t e n c e o f f o e t a l i n f e c t i o n d u r i n g i n t r a - u t e r l n e life. T h e p r e s e n t a r t i c l e deals w i t h 3 m o r e cases in w h i c h t h e p r e s e n c e o f c o n g e n i t a l t u b e r c u l o s i s has b e e n p r o v e d in y o u n g infants o n c l i n i c a l a n d p a t h o l o g i c a l examinations.
Case Reports Case l A 3-week-old female child was admitted to the children's ward of the Hadas;ah-University Hospital, for severe respiratory distress and cyanosis. Both parents and their 2o-months-old first child, were healthy. A paternal aunt had been found to have pulmonary tuberculosis three 3"ears before, but her disease was clinically arrested and the sputum negative before the birth of the present child. The delivery of the patient was normal following an uneventful pregnancy. The weight at birth was ~,76o g. and the breast-fed child gained weight during the next two weeks. Five days prior to admission the child developed a cold and refused food. During the next few days progressive respirator)' distress developed until admission. On admission the pertinent findings were severe respiratory distress and cyanosis. Moist rfiles were heard all over both lungs. The child was put in art oxygen tent and given antibiotics. During the subsequent three days the temperature ranged up to 39°C. (lo~ ° F.) and there was no change in the respiratory status. X-ray examination revealed an intense mottling of both lungs. The child dled on the fourth day after admission, at the age of 4 weeks, with a diagnosis of bilateral pneumonia. .tVecrol,sy Findings.- The body was that of a female child x~cighlng ~,85o g. The essential gross findings were confined to the lungs. The pleural surface of the lungs was studded with greyish-wlfite. nodules measuring x-8 ram. in diameter. The consistency of the remaining lung tissue was increased. On cut surface the nodules were scattered throughout both lungs, leaving only a small amount of intact lung tissue. Some of the nodules were softer and on pressure oozed ~ome light-yellowish material. A similar material was contained within the main bronchi and trachea. The hilar and carinal lymph nodes were slightly enlarged. The spleen and liver were congested. Histological Exambzation.- The greyish nodules in the lungs were composed of an amphophilic material surrounded by an inflammatory cellular cxudate. In some sections the lesions were bronehopneumonie in form, the bronchioles and the surrounding alveoli being filled with granulocytes and mononuelear cells. No typical tubercles or giant cells were found, but all the lesions in the lungs swarmed with acid-fast bacilli. In a few alveoli signs of amniotic fluid aspiration were found, indicated by the presence of cornified material, presumably originating from the foetal epidermis. The tfilar and carinal lymph nodes were the gite of caseous necrosis and round cell and granulocytic infiltration. In the liver and spleen a few loci of necrosis and an occasional giant cell were found. In all the necrotic loci acid-fast bacilli were demonstrated. Subsequent Maternal History.-After tuberculosis was revealed at the child's post-mortem the mother was re-examined. On repeated endometrial biopsies by histological and bacteriological
CONGENITAL "TUBERCULOSIS
167
examinations, tuberculous endometritis was found. She was treated with streptomycin and PAS for the next eight months, until culture and histological examination of the endometrium gave normal results. Repeated x-ray studies of the chest and cultures of the sputum were always negative. Cases 2 and 3
A 36-year-old woman, known to be suffering from widespread tuberculosis, gave birth to twins in tile seventh month of pregnancy. The babies were separated from the mother immediately after birth and placed in incubators. The infants weighed 1,8oo g. each. Bah)" A died at the age of 23 days without clinical evidence of illness. Baby B had a bout of fever and on x-ray examination there was diffuse mottling of both lungs. It died at the age of 33 days. The mother died shortly after delivery and generalized tuberculosis of lungs, abdominal and pelvic organs was found at necropsy. Baby A (Case 2 ) . - The necropsy findings of Baby A were chiefly confined to the lungs. Both lungs were studded with tiny grey nodules. Histological examination of the lungs revealed that the nodules were composed of caseous material surrounded by round-cell infiltration, but no giant cells. Tim lesions were situated intra-alveolarly and in alveolar walls and only occasionally were bronclfioles involved. All the lesions contained numerous acld-fast bacilli and phagocytosed acidfast granules. The hilar lymph nodes showed caseating loci and epithefioid tubercles. In the liver several small foci of granulomatous infiltration were found. Baby B (Case 3 ) - - I n Baby B widespread tuberculous involvement of lungs, liver, spleen and lxmph nodes was found. These organs were studded with grey nodules x-2 ram. in diameter. In the lungs tllere were some areas wilere the nodules were confluent. Histologically, the findings in the lungs were similar to those of Baby"A. In addition, typical tubercles with giant ceils were found and there was invoh'ement of bronchial walls; some tubercles were seen in the intima of veins. The hilar and mesenteric 1)wnph nodes were the site of easeating tubercles. The entire liver parenchyma was studded with tubercles showing caseation necrosis. Acid-fast bacilli were found in all these lesions. In the kidneys tubercles with giant cells were seen. In the brain and meninges there were loci of round cell and leucocytic infiltration.
Comment I n a recent review, C o r n e r a n d Brown (I955) re-stated the criteria of Beitzke (I935) for the diagnosis of congenital tuberculosis: T h e lesion in the child m u s t be proved to be tuberculous. E x t r a - u t e r i n e infection m u s t be excluded b y d e m o n s t r a t i n g e i t h e r (a) the presence of tuberculous lesions at birth, or (b) a p r i m a r y complex in the liver a n d regional nodes, or (c) the child m u s t have been i m m e d i a t e l y separated from the m o t h e r a n d other possible sources o f infection. All 3 c h i l d r e n a n d both mothers presented here h a d proved tuberculous lesions o n histological a n d bacteriological study. Cases 2 a n d 3, the twins, were separated from the m o t h e r i m m e d i a t e l y after birth. A l t h o u g h the first infant h a d not been removed from the m o t h e r i m m e d i a t e l y after birth, we believe t h a t extra-uterine infection can be excluded because: (x) th~ d e v e l o p m e n t of such extensive p u l m o n a r y lesions w o u l d require a longer period t h a n the four weeks of post-natal life (Reichle a n d Wheelock, i939). (2) Tuberculosis in the m o t h e r was proven to be confined to the genital organs, thus e l i m i n a t i n g the possibility of post-natal infection (Hertzog a n d others, i949). T h r e e possible routes of i n t r a - u t e r i n e transmission of tuberculous infection have been suggested in previous publications. I n b l o o d - b o r n e infections the bacilli pass t h r o u g h the p l a c e n t a into the u m b i l i c a l vein, a n d a p r i m a r y complex is formed i n the foetal liver a n d portal l y m p h nodes. Sometimes, the b l o o d - b o r n e bacilli m a y by-pass the liver t h r o u g h the ductus venosus, a n d a p r i m a r y complex m a y form in the lungs. T h e other routes involve either swallowing or aspirating infected a m n i o t i c fluid. I n the first instance, p r i m a r y intestinal tuberculosis would develop, a n d in the latter a widespread p u l m o n a r y infection would result. I n the latter case the lesion would be confined to the lungs, b u t later i n v o l v e m e n t of hilar l y m p h nodes a n d even a h a e m a t o g e n o u s spread m i g h t occur (Horley, i95~ ). We presume that the route of infection in our first case was most p r o b a b l y b y aspiration of a m n i o t i c fluid. T h e severest lesions were found i n the lungs a n d there
I68
TUBERCLE
was a b r o n c h o p n e u m o n i c s p r e a d ; k e r a t i n scales p r o b a b l y o r i g i n a t i n g from the a m n i o t i c fluid w e r e p r e s e n t w i t h i n the e x u d a t e . I n a d d i t i o n , t h e r e was a s e c o n d a r y tuberculous s p r e a d to h i l a r l y m p h nodes a n d evidence o f h a e m a t o g e n o u s s p r e a d to t h e liver a n d spleen. I n Case 2 ( B a b y A ) , t h e findings w e r e s o m e w h a t s i m i l a r to those o f Case I a n d suggested a s p i r a t i o n as t h e r o u t e o f infection. T h e lack o f a p r i m a r y c o m p l e x in the liver or lungs w o u l d speak against t b e h a e m a t o g e n o u s route o f infection. T h e absence o f gastro-intestinal lesions e x c l u d e d swallowing o f a m n i o t i e fluid as the r o u t e of infection. I n the t h i r d case ( B a b y B), the i n v o l v e m e n t was so w i d e s p r e a d a n d b o t h ' e a r l y a n d late changes were seen in all the organs, t h a t no conclusions as to t h e r o u t e o f infection could b e d r a w n . T h e final d i s s e m i n a t i o n was b y the blood s t r e a m a n d tubercles could b e shown in t h e i n t i m a o f p u l m o n a r y veins. I t has b e e n n o t e d b y some investigators that, even i f tuberculous lesions are f o u n d in" tile p l a c e n t a , n o t all the c h i l d r e n b o r n o f tuberculous m o t h e r s d o b e c o m e infected in utero ( C a l m e t t e , cited b y R i c h , x95i ). T h i s has b e e n a t t r i b u t e d to resistance o f the foetus d u e to t h e low o x y g e n tension o f t h e foetal blood (Rich, 1951 ; R i c h a n d Follis, 1942; V o n v a l d , i937).
Summary T h r e e cases o f c o n g e n i t a l tuberculosis a r e presented, 2 being in twins. T i l e cases fulfil the c r i t e r i a o f Beitzke for the diagnosis o f c o n g e n i t a l tuberculosis. I n Case i the r o u t e o f the i n t r a - u t e r i n e infection was b y aspiration, in the o t h e r 2 cases either b y a s p i r a t i o n or t h r o u g h the b l o o d s t r e a m . Tile authors wish to thank Dr Hupert from the Beth Meir Hospital and Prof Casper from the Pathological Institute, Beilinson Hospital, for their kind help and permission to publish Cases 2 and 3, and Drs Mendes and Toaf for their kind information concerning Case I. We also wish to acknowledge the helpful interest of Prof Ungar, Head of Dept. of Pathology, Hebrew UniversityHadassah Medical School.
References Beitzke, H. (x935) Ergebn. ges. TuberkForsch., 7, i. Breton, A., and Dubois, O. 0955) Echo mgd. Word.., 26, 233. Comer, B. D., and.Brown, N.J. 0955) Thorax, xo, 99. Debre, R., Furiet-Laforest, - . , and Royer, P. (x948) Arch.fran9. Pgdiat., 5, °55Dubsky, F. 0955) Canad. reed. Ass. J., 73, 66~. Hertzog, A. J., Chapman, S., and Herring, J. 0949) Amer. o7. din. Path., x9, I x39. Horley, J. F. (x952) Arch. Dis. Childh., ~7, x67. Hudson, F. P. 0956) Arch. Dis. Childh., 3t, 136. Lelong, M. R., Rnssler, A., Laumonier, R., and Roussel, A. (x954) Arch. Anat. apth., 3o, t86. Ormos, J., and P~ldy, L. 0955) 22bl. allg. Path. path. Anat., 94, xx7. Ra}temacher, M. 0955) Kinderiirztl. Prax., ~3, ~98Ravina, J., and Daunay, J . J . (i 955) Bull. F/d. Gyn/c. Obstet.franf., 7, 41 x. Reichle, H. S., and Wheelock, M. C. 0939) Arch. Path., 28, 799Rich, A. R. (I951) The Pathogenesls of Tuberculosis, ~nd edition, Blackwell Scientific Publications, Oxford. Rich, A. R., and Follis, R. H., Jr. (x94a) JohnsHopk. Hosp. Bull., 7 x, 345. Riordan, T. P. 0955) N.Z. reed. J., 54, 568. Romagny, G., Fontvielle, J., and Esclangon, - . 0956) Pediatric, xx, 594. Vorwald, A.J. 0937) Amer. Rev. Tuberc., 35, 26o.