- Email: [email protected]
Congenital Malformations
REV IEW O F 1957 DEN T A L R ESEA R C H . . . V O L U M E 56, M A Y I9S8 • 633
seem to show that the organisms respon sible for the carious destruction o f enamel in man are a relatively small group within the family Lactobacteriaceae, and that the most active organism is the alphahemolytic streptococcus, with some con tribution from the relatively fewer lacto bacilli. Carious lesions have been produced by pure cultures of various other organisms in animals and in vitro.25,26 C L IN IC A L A S P E C T S
Interesting reports have been published on the rate of progression of the carious lesion,27 on the incidence of caries on various teeth,28 on the effect of carbo hydrates on caries,29 and on salivary cit rate and caries.30 M IS C E L L A N E O U S A S P E C T S
The mineralization of teeth;81,82 the role of dietary carbohydrate in the develop ment of caries resistance ;33,34 the positive relation of salivary protease in rats35 and the absence of relation of certain salivary constituents to caries in m an;36 a method of autoradiography of teeth,37,38 the
chemical,39 and histological40 behavior of brown pigmentation have been de scribed, and also the production of arti ficial caries in sugar solutions.41
30. Z ip k in , I., a n d o th e rs. T he r e la t io n o f s a liv a r y c it r a t e to d e n t a l c a r ie s e x p e r ie n c e in c h ild r e n 12 t o 14 ye a rs o ld . J . D. Res. 36:823 D e c . 1957. 31. B e la n g e r, L. F. M in e r a l iz a t io n o f ra t e n a m e l in th e lig h t o f C a - 4 5 a u t o r a d io g r a p h y a n d m ic r o in c in e r a tio n . J . D. Res. 36:595 A u g . 1957. 32. E n g fe ld t , Bencgt, a n d H a m m a r lu n d - E s s le r , E rn a . S t u d ie s o n m in e r a liz e d d e n t a l t issu e s. X . A m ic r o r a d i o g r a p h i c , a u t o r a d io g r a p h ic a n d h is t o c h e m ic a l in v e s t ig a t io n o n d e n t a l h a rd t is su e s in d o g s w ith e x p e r i m e n t a lly p r o d u c e d v it a m in D d e fic ie n c y . A c t a O d o n t . S c a n d in a v . 14:293 J a n . 1957. 33. B u x b a u m , J. D., a n d o th e rs . E ffe ct o f d ie t on the d e p o s it io n o f g l y c o p r o t e in In th e tee th a n d its r e la t io n s h ip to d e n t a l c a r ie s in th e S y r ia n h a m s te r. J. D . Res. 36:173 A p r i l 1957. 34. S t e in m a n , R. R., a n d H a le y , M . I. E a r ly a d m i n i s t r a t io n o f v a r io u s c a r b o h y d r a i e s a n d s u b s e q u e n t d e n t a l c a r le s in th e rat. J. D . Res. 36:532 A u g . 1957. 35. W ille t t , N . P., a n d o th e rs . C o m p a r is o n o f s a liv a r y p r o t e a s e a c t iv it y in t h e H u n t - H o p p e r t c a r ie s - r e s is t a n t a n d c a r ie s - s u s c e p t ib le rats. J . D . Res. 36:223 A p r i l 1957. 36. Z ip k in , I.; B u llo c k , F. A . , a n d M a n t e l, N . t io n o f _ s a liv a r y s o d iu m , p o t a s s iu m , s o l id s a n d a sh c e n tr a tio n t o d e n t a l c a r ie s e x p e r ie n c e In c h ild r e n , 6 a n d 12 t o 14 y e a r s o f a g e . J . D. Res. 36:525 A u g .
R e la con 5 to 1957.
37. B o y d , J. D . D e n ta l a u t o r a d io g r a p h y . I. C h o i c e o f r a d io is o t o p e . J . D . Res. 36:274 A p r i l 1957. 38. B o y d , J. D .; S im s, R. W . , a n d O s g o o d , D . R. D e n ta l a u t o r a d io g r a p h y . I I . E ffe c t o f p r in t in g t e c h n ic s o n in t e r p r e t a tio n . J . D . Res. 36:281 A p r i l 1957. 39. D re iz e n , S., a n d o th e rs. E x p e r im e n t a l o b s e r v a t io n s o n m e la n o id in f o r m a t io n in h u m a n c a r io u s te e th . J . D. Res. 36:233 A p r i l 1957. 40. B hu ssry, B. R., a n d B ib b y , B. G . S u r f a c e In e n a m e l. J . D . Res. 36:409 J u n e 1957.
changes
41. M u r a c c io l e , J . C ., a n d D o m in g u e z , A . T h e p r o d u c t io n o f e x p e r im e n t a l c a r ie s b y s o lu t io n s c o n t a in in g re fin e d c a r b o h y d r a t e s . R e v. A . O d o n t . A r g e n t in a 45:281 A u g . 1957.
C O N G E N IT A L M A L F O R M A T IO N S Samuel Pruzansky, D.D.S., Chicago There are many reasons for the upsurge of interest in congenital malformations; first, because the general problem of causality of congenital malformations in man has become a matter of concern not only to the scientific community but to all who share in responsibility for the conduct of human affairs. This wide spread interest stems from the debate on the genetic effects o f man-made radiation. In 1957, this concern was displayed in newspapers and lay magazines as well as in scientific journals.
There are other reasons, less dramatic but more tangible, that account for the attention given to human malformations. According to a review by Warkany,1 the profile of pediatric practice is changing. With the continued reduction in peri-
A s s o c ia t e p r o f e s s o r o f o r t h o d o n t ic s , S c h o o l o f D e n tistry, U n iv e r s it y o f Illin o is ; a s s o c ia t e d ir e c t o r , c le ft p a la t e c lî n î c t C e n t e r f o r H a n d i c a p p e d C h ild r e n , C h i c a g o P r o fe s s io n a l C o l le g e s , U n iv e r s it y o f Illin o is . I. W a rka n y , a tric s . P e d ia t r ic s
J. C o n g e n i t a l m a lf o r m a t io n s a n d p e d i 19, P a rt 2:725 A p r i l
1957.
634 • T H E J O U R N A L O F T H E A M E R IC A N D EN T A L A S S O C IA T IO N
natal mortality, more attention is focused on every baby death. Congenital malformations now ac count for about 14 per cent of all infant deaths in the United States. In New Zealand, where infant death rates are lower than in the United States, congeni tal malformations at the present time contribute 20 per cent to the general infant mortality. The incidence and importance of con genital malformations cannot be estab lished by mortality statistics alone. Many congenital malformations are undetected until later in life when they are un masked by illness or the development of functional deficits. For example, congeni tal palatal insufficiency is rarely sus pected until the child begins to speak with excessive hypernasality or else the anomaly is unmasked by adenoidectomy.2 The nature o f other congenital malfor mations is such that the child survives only to require continued hospitalization or confinement within the home. In others, successful habilitation as self-sustaining individuals is achieved only as a result of elaborate medical and dental care and special education. For dental science, congenital mal formations of the head offer a challenge and an opportunity.3 The challenge is in the treatment of such patients and the opportunity is in research. These “ experi ments o f nature” on fellow creatures, if properly considered, will yield new and useful knowledge far beyond the patients and the anomalies studied. CASE REPO RTS
As in every other year, the world litera ture contained numerous case reports of human teratomas. In the main, these were o f no special interest for dental science except for reports of cranial defects4 and intraoral5,6 and nasal7,8 dermoid cysts. Pleydell9 reported on an epidemiologi cal study in Northamptonshire of four types of malformations of unknown etiol
ogy— mongolism, congenital malforma tions of the heart, cleft lip and cleft palate, and major malformations of the central nervous system. On the basis of the variable incidence reported from year to year in the same locale, the author sug gested the operation of some inconstant environmental factor such as infection. C ON FEREN CE ON TERATOLOGY
The outstanding publication of the year in the field of teratology was the special supplement to the April 1957 issue of Pediatrics which was devoted to the pro ceedings of a conference on congenital malformation held in Cincinnati, Ohio, in January 1956. At this conference, Patten10 reviewed developmental mechanisms involved in teratogenesis as a basis for a discussion on possible etiologic factors. He pointed out that the concept of “ developmental arrest,” although adequate in explaining cleft lip and cleft palate, failed to ac count for many other defects. Five other mechanisms leading to developmental aberrations were described and the con clusion drawn that it was futile to try to
2. Lis, E. F. The c h ild with c le ft lip a n d c le ft p a la t e . In M a n a g e m e n t o f th e h a n d ic a p p e d c h ild . M ic h a l S m ith , H ., e d it o r . N e w Y o r k , G r u n e & S tra tto n , 1957. 3. P ru zan sk y, S. F o u n d a t io n s o f th e c le ft p a la t e c e n te r a n d t r a in in g p rogra m a t th e U n iv e r s it y o f Illin o is . A n g l e O r t h o d o n t . 27:69 A p r i l 1957. 4. K a p p e r s , J. A . D e v e lo p m e n t a l d is t u r b a n c e o f th e b r a in in d u c e d b y G e r m a n m e a s le s in a n e m b r y o o f th e 7th w e e k . A c t a A n a t . 31:1, 1957. 5. K o t e r la , B. P r z y p a d e k ustne j. ( In t r a - o r a l d e r m o id 12:522 N o v . 1957.
t o r b ie li sk o rz a ste j ja m y c yst.) P o lsk i T y g o d . Lek
6. A le s s i, R. Su un c a s o d i c is ti d e r m o id e g i g a n t e d e l p a v im e n t o d e lla b o c c a ; s t u d io a n a t o m y - t o p o c j r a fic o d e lla r e g io n e s u b lin g u a le , a n a to m o , p a t o l o g ic o e c lin ic o . ( C a s e o f g i a n t d e r m o id c y st o f th e f lo o r o f t h e m o u th ; a n a t o m i c o - t y p o g r a p h ic s t u d y o f th e s u b lin g u a l r e g io n , p a t h o l o g ic a n a to m y and c lin ic a l a s p e c t s . ) M in e r v a C h ir . T o r. 12:308 N o v . 1957. 7. V e rs c h u y l, E.; G r e e p , J . M ., a n d V e r s c h u y l, M . A . A a n g e b o r e n d e r m o id k y s t e n v a n d e n e u s. ( C o n g e n i t a l d e r m o id c ysts o f the n o se .) N e d . T sch r. G e n e e s k . 101:1116 N o v . 1957. 8. F e rra ttI, C . d e r m o id c ysts.) 1957.
E. Q u is t e s d e r m o id e s n a s a le s . ( N a s a l B ol. S o c . d r . U r u g u a y 26:271 N o v .
9. P le y d e ll, M . J . M o n g o l is m _ a n d o th e r a b n o r m a lit ie s : an e p i d e m i o l o g ic a l stu d y h a m p t o n s h ir e . L a n c e t 272:1314 1957.
June
c o n g e n it a l N orth -
in
10. P atten , M . V a r y in g d e v e lo p m e n t a l m e c h a n is m s in t e r a t o lo g y . P e d ia t r ic s 19, P a rt 2:734 A p r i l 1957.
R EV IEW O F 1957 DEN T A L R ESEA R C H . . . V O L U M E 56, M A Y 1958 • 635
find an all-encompassing cause of con genital defects. Patten suggested that de ficiency factors might account for the ‘developmental arrest” type, whereas regulatory factors and disturbances in timing can account for the other cate gories. E X P E R IM E N T A L T E R A T O G E N E S IS
The artificial production of abnormali ties, identical with those arising as the result of gene action, is not only interest ing by virtue of the end result but be comes a useful tool in revealing the mechanisms underlying normal and ab normal processes of development. Pres ent trends in experimental mammalian teratology reveal an expansion of interest from the# morphologic study of abnormal embryos11 and offspring12 for abnormali ties o f physiology13,14 and biochemistry 15,16 l mmunologic phenomena17 and infectious agents18 are also being con sidered. Different teratogenic agents have pro duced artificial counterparts to almost all genetically caused abnormalities. H ow ever, Gluecksohn-Waelsch17 warned that the resemblance of effects produced by different agents, genetic or environ mental, does not necessarily imply actual resemblance of causal mechanisms but rather indicates a resemblance in the function of the reacting system. Thus, the similarity of cortisone-induced and genetically caused cleft palate does not mean that the genetically abnormal in dividual suffers from an excess of corti sone. Instead, it indicates that the mate rial forming the palate is, at a particular stage, susceptible to cortisone as well as to an unknown factor acting on a genetic basis. The question of specificity in experi mental teratology was reviewed by W il son.19 Time-specific effects were demon strated best when minimal effective dosages of various teratogenic agents were used. Agent-specificity was more
difficult to establish from available ex periments because of variability in dosages employed, species studied, age at which the offsprings were examined, and the influence of special interest on the part of the investigator. Nelson20 summarized the information derived from the production of congeni tal anomalies in mammals by maternal dietary deficiencies. The similarity of anomalies resulting from dietary and other teratogenic procedures was strik ing. Acute dietary deficiencies brought on by the use of antimetabolites indicated that the effect usually was limited to the critical period of differentiation and organogenesis, as it is in irradiation. Studies on the inter-relations o f nutri tional and genetic factors were urged as a means of determining individual sus ceptibility to teratogenic conditions. Walker and Fraser21 reported on the embryology of cortisone-induced cleft palate in two strains of mice. They de termined that cortisone treatment caused cleft palate by interfering with the de-
11. M o h a m m e d , C . I. G r o w t h p a t t e r n o f th e rat m a x illa f r o m 16 d a y s in s e m in a t io n a g e to 3 0 d a y s a fte r b ir t h . A m . J. A n a t . 100:115 J a n . 1957. 12. J u lia n , L ; fvj., a n d o th e rs. P r e m a tu r e c lo s u r e of th e s p h e n o - o c c ip it a l s y n c h o n d r o s is in th e h o r n e d H e r e fo rd d w a r f o f th e " s h o r t - h e a d e d " v a r ie t y . A m . J. A n a t . 100:269 M a r c h »957. 13. W o o ll a m , D . H ., a n d M ille n , J . W . E ffe ct o f c o r t is o n e o n t h e in c id e n c e o f c le ft p a la t e in d u c e d b y e x p e r im e n t a l h y p e r v it a m in o s is A . B rit. M e d . J . 5038:197 J u ly 27, 1957. 14. In g a lls , T. H ., a n d C u r le y , F. J . T he re la t io n o f h y d r o c o r t is o n e in j e c t io n s t o c le ft p a la t e in m ic e . N . E n g l a n d J . M . 256:1035 M a y 30, 1957. 15. N e ls o n , M . M ., a n d o th e rs . T e r a t o g e n ic e ffe c ts o f p a n t o t h e n ic a c i d d e f ic ie n c y in th e rat. J . N u t r it io n 62:395 J u l y 1957. 16. M o n ie , I. W . ; N e ls o n , M . M ., a n d E van s, H . M . A b n o r m a l it i e s o f th e u r in a r y sy ste m o f ra t e m b r y o s r e s u lt in g f r o m t r a n s it o r y d e f ic ie n c y o f p t e r o y lg lu t a m ic a c i d d u r i n g g e s t a t io n . A n a t . R e c . 127:711 A p r i l 1957. 17. G lu e c k s o h n - W a e ls c h , S. T r e n d s in m a m m a lia n t e r a t o lo g y . P e d ia t r ic s 19, P a rt 2:7 77 A p r i l 1957. 18. G a b k a , J. T ie r e x p e r im e n t e lle U nte rsu ch u n ge n zu r E r z e u g u n g v o n P h ä n o k o p ie n d u r c h t o x o p la s m e n in fe k t io n . ( E x p e r im e n t a l re s e a r c h o n in d u c t io n o f p h e n o c o p y t h r o u g h t o x o p la s m o s is in fe c t io n .) Z s c h r . m e n sch !. V e r e r b . 34:38 N o v . 1957. 19. W ils o n , J . G . Is th e r e s p e c if ic it y o f a c t io n in e x p e r im e n t a l t e r a t o g e n e s i s ? P e d ia t r ic s 19, P a rt 2:755 A p r i l 1957. 20. N e ls o n , M. M. P r o d u c t io n of c o n g e n it a l a n o m a l ie s in m a m m a ls b y m a t e r n a l d ie t a r y d e f ic ie n c ie s. P e d ia t r ic s 19, P a r t 2:764 A p r i l 1957. 21. W a lk e r , B. E., a n d F ra se r, F. C . T he e m b r y o l o g y o f c o r t is o n e - in d u c e d c le ft p a la t e . J . E m b r y o l. E x p . M o r p h . 5:201 J u n e 1957.
636 • THE J O U R N A L O F THE A M E R IC A N D EN T A L A S S O C IA T IO N
velopment of the condition within the palatine shelves that forces them to change their alignment from the vertical to the horizontal plane. The difference between the two strains in their suscepti bility to the teratogenic action o f corti sone was due in part to the earlier closing o f the palate and lesser inhibition of shelf movement observed in the less susceptible strain of mice. The results of 50 transabdominal amniocenteses in normal human beings during the last two trimesters of preg nancy were reported without evidence of maternal or fetal trauma.22 The contrast to the high incidence of congenital mal formations produced by amniotomy in mice was related to the stage o f preg nancy in which amniocentesis was per formed and the ratio of fetal volume to amniotic fluid in various species. G E N E T IC H A Z A R D S OF R A D IA T IO N
The genetic effects o f radiation on man continued to provoke profound concern among scientists. Crow,23 in theorizing on the mutagenic effects of roentgen rays, gave some crude estimates of the genetic effect to be expected from 10 r of radia tion (the amount recommended as the maximum average gonad dose for the population). Dobzhansky24 wrote, “ as far as genetic effects are concerned, the only safe dose of high-energy radiation is no radiation.” This view was shared by other geneticists.26,26 A recent statement by the United Na tions Scientific Committee on the Effects of Atomic Radiation about the responsi bilities of the medical profession in the use of roentgen rays and other ionizing radiation was a step in the direction of controlling irradiation of human beings.27 An editorial statement28 in t h e j o u r n a l OF
THE
A M E R IC A N
DENTAL
A S S O C IA T IO N
gave reassuring information regarding the minimal gonadal exposure during conventional dental roentgenographic ex amination.
G E N E T IC F A C T O R S
The interaction o f genetic and environ mental factors has been demonstrated on drosophila by Goldschmidt and Piternick,29 and on several strains of mice by Kalter,30 and Fraser and his associates.31 Recently, geneticists have become in terested in American triracial isolates.32 Because of several centuries of in-mar riage, many genetically recessive traits have become manifest and many geneti cally dominant traits have become con centrated in a few families. An excep tionally high incidence of dentinogenesis imperfecta and other hereditary condi tions has been reported in these groups.33 Witkop’s34 survey o f hereditary defects of enamel and dentin in the general popula tion of children allows for interesting comparison with the triracial isolates. Neel35 suggested several useful lines of attack on the genetic aspects o f human teratology. Included were the methods of comparative teratology to determine if
22. P arrish , H . M .; L o c k , F. R., a n d R o u n tre e , M . E. L a c k o f c o n g e n it a l m a lf o r m a t io n s in n o r m a l h u m a n p r e g n a n c ie s a fte r t r a n s a b d o m in a l a m n io c e n t e s is . S c ie n c e 126:77 J u l y 12, 1957. 23. C r o w , J a m e s F. P o s s ib le c o n s e q u e n c e s o f a n in c r e a s e d m u ta tio n rate . E u g e n ic s Q u a r t e r ly 4:67 J u n e 1957. 24. D o b z h a n s k y , T. G e n e t i c lo a d s în t io n s . S c ie n c e 126:191 A u g . 2, 1957. 25. G la s s , B. T h e g e n e t ic h a z a r d s t io n s. S c ie n c e 126:241 A u g . 9, 1957. 26. J a p a n e s e g e n e t ic is t s o n J u ly 12, 1957. 27. U . N . a n d M a r c h 29, 1957.
m e d ic a l
of
n atu ra l
p o p u la
n u c le a r
r a d ia t io n . S c ie n c e
i r r a d ia t io n .
S c ie n c e
ra d ia 126:28 125:592
28. G o n a d a l r a d ia t io n in c id e n t a l t o d e n t a l ro e n t g e n o l o g y a p p e a r s t o b e r e la t iv e ly i n s ig n if ic a n t . J . A . D . A . 55:722 N o v . 1957. 29. G o l d s c h m i d t , R. B., a n d P ite rn ic k , L. K . T he g e n e t ic b a c k g r o u n d o f c h e m ic a l ly in d u c e d p h e n o c o p ie s in d r o s o p h il a . J. Exp. Z o o l . 135:127 J u n e 1957. 30. K a lte r, H . F a c t o r s in f lu e n c in g t h e f r e q u e n c y o f c o r t is o n e - in d u c e d c le ft p a la t e in m ic e . J . E x p . Z o o l. 134:449 A p r i l 1957. 31. F ra se r, F. C . ; W a lk e r , B. E., a n d T ra s le r, D . G . E x p e r im e n t a l p r o d u c t io n o f c o n g e n it a l c le ft p a la t e : g e n e t ic a n d e n v ir o n m e n t a l f a c t o r s . P e d ia t r ic s 19, P a rt 2:782 A p r i l 1957. 32. B eale , C a l v in L. A m e r i c a n t r î- r a c îa l iso la te s: t h e ir sta tu s a n d p e r t in e n c e t o g e n e t ic r e s e a r c h . E u g e n ic s Q u a r t e r ly 4:187 D e c . 1957. 33. W i t k o p , C . J. A s t u d y o f t r i- r a c ia l E a ste rn U n it e d S ta te s. A c t a G e n e t . 6:410,
is o la t e s 1956/7.
in
34. W i t k o p , C . J . H e r e d i t a r y d e f e c t s in e n a m e l a n d d e n t in . A c t a G e n e t . 7:236, 1957. 35. N e e l, J . V. G e n e t ic s a n d h u m a n c o n g e n it a l m a l fo rm a t io n s . P e d ia t r ic s 19, P a r t 2:749 A p r i l 1957.
R EV IEW O F 1957 D EN T A L R ESEA R C H . . . V O L U M E 56, M A Y 1958 • 637
diet and disease are important factors in the statistics of malformations among various peoples; a detailed study of par ents o f affected children, and detailed studies of similarities among siblings with a given defect. Fraser,36 in search of etiologic factors in cleft lip and cleft palate, found that mothers o f such children demonstrated a higher frequency o f pathologic condi tions in the reproductive tract.
C O N C L U S IO N S
The evidence now available stresses the multiplicity and inter-relatedness of etiologic factors as well as the variety of developmental mechanisms involved in the production of congenital malforma tions.
36. F ra se r, F. C . E t i o l o g ic a l f a c t o r s in p a la t e a n d lip . A c t a . G e n e t . 7:229, 1957.
c le fts o f the
R E S E A R C H A N D E D U C A T IO N Paul E. Boyle, D .M .D ., Cleveland Research is concerned with the acquisi tion o f knowledge. Education is the proc ess by which knowledge is passed on to succeeding generations. Volumes have been written on the subject, and it has challenged superior minds from Plato and Aristotle to Whitehead and Hutchins. The primary concern o f this report is the relation of research to education and its bearing on dentistry, including its specialty groups. A brief comment on education in general may be in order before discussing research and the mutual relation of one to the other. In embryology, the statement “ ontogeny recapitulates phylogeny” concisely sum marizes the complex processes o f develop ment. A single cell multiplies, grows, and differentiates, passing through stages reminiscent of ameba, coelenterate, fish and reptile, before finally assuming recog nizable human form. Education is an other complex process through which the squalling infant and the rebellious child become adult, mature members o f so ciety. The momentous changes in the first few weeks of intra-uterine life are more important than anything occurring later in physical development. In much the same way, experiences in infancy and
early childhood are of major significance in the evolution of behavior patterns and emotional characteristics. It is meanipgful to the dental profession that one of the most important instincts of a new born baby is concerned with the mouth. Suckling, contact with the mother and through her with the outside world are functions of a primitive part o f the brain. The sucking reflex is found even in anencephalic monsters. In these formative years the child’s re lation to his mother is paramount. School involves adjustment to a larger circle of adults as well as to others of the same age group. The success with which these ad justments are made depends on the en vironment, the skill o f the teacher and, most of all, on the early experiences of the child. Undue aggressiveness, anxiety, over-dependence, or other behavior prob lems may first manifest themselves at this stage of education, though their roots lie in infancy. The American ideal of equality o f op portunity led to the establishment of public schools. This was a major change from Europe where education was a
D e a n , S c h o o l o f D e n tistry , W e s t e r n R e se rv e U n iv e rs it y .
seem to show that the organisms respon sible for the carious destruction o f enamel in man are a relatively small group within the family Lactobacteriaceae, and that the most active organism is the alphahemolytic streptococcus, with some con tribution from the relatively fewer lacto bacilli. Carious lesions have been produced by pure cultures of various other organisms in animals and in vitro.25,26 C L IN IC A L A S P E C T S
Interesting reports have been published on the rate of progression of the carious lesion,27 on the incidence of caries on various teeth,28 on the effect of carbo hydrates on caries,29 and on salivary cit rate and caries.30 M IS C E L L A N E O U S A S P E C T S
The mineralization of teeth;81,82 the role of dietary carbohydrate in the develop ment of caries resistance ;33,34 the positive relation of salivary protease in rats35 and the absence of relation of certain salivary constituents to caries in m an;36 a method of autoradiography of teeth,37,38 the
chemical,39 and histological40 behavior of brown pigmentation have been de scribed, and also the production of arti ficial caries in sugar solutions.41
30. Z ip k in , I., a n d o th e rs. T he r e la t io n o f s a liv a r y c it r a t e to d e n t a l c a r ie s e x p e r ie n c e in c h ild r e n 12 t o 14 ye a rs o ld . J . D. Res. 36:823 D e c . 1957. 31. B e la n g e r, L. F. M in e r a l iz a t io n o f ra t e n a m e l in th e lig h t o f C a - 4 5 a u t o r a d io g r a p h y a n d m ic r o in c in e r a tio n . J . D. Res. 36:595 A u g . 1957. 32. E n g fe ld t , Bencgt, a n d H a m m a r lu n d - E s s le r , E rn a . S t u d ie s o n m in e r a liz e d d e n t a l t issu e s. X . A m ic r o r a d i o g r a p h i c , a u t o r a d io g r a p h ic a n d h is t o c h e m ic a l in v e s t ig a t io n o n d e n t a l h a rd t is su e s in d o g s w ith e x p e r i m e n t a lly p r o d u c e d v it a m in D d e fic ie n c y . A c t a O d o n t . S c a n d in a v . 14:293 J a n . 1957. 33. B u x b a u m , J. D., a n d o th e rs . E ffe ct o f d ie t on the d e p o s it io n o f g l y c o p r o t e in In th e tee th a n d its r e la t io n s h ip to d e n t a l c a r ie s in th e S y r ia n h a m s te r. J. D . Res. 36:173 A p r i l 1957. 34. S t e in m a n , R. R., a n d H a le y , M . I. E a r ly a d m i n i s t r a t io n o f v a r io u s c a r b o h y d r a i e s a n d s u b s e q u e n t d e n t a l c a r le s in th e rat. J. D . Res. 36:532 A u g . 1957. 35. W ille t t , N . P., a n d o th e rs . C o m p a r is o n o f s a liv a r y p r o t e a s e a c t iv it y in t h e H u n t - H o p p e r t c a r ie s - r e s is t a n t a n d c a r ie s - s u s c e p t ib le rats. J . D . Res. 36:223 A p r i l 1957. 36. Z ip k in , I.; B u llo c k , F. A . , a n d M a n t e l, N . t io n o f _ s a liv a r y s o d iu m , p o t a s s iu m , s o l id s a n d a sh c e n tr a tio n t o d e n t a l c a r ie s e x p e r ie n c e In c h ild r e n , 6 a n d 12 t o 14 y e a r s o f a g e . J . D. Res. 36:525 A u g .
R e la con 5 to 1957.
37. B o y d , J. D . D e n ta l a u t o r a d io g r a p h y . I. C h o i c e o f r a d io is o t o p e . J . D . Res. 36:274 A p r i l 1957. 38. B o y d , J. D .; S im s, R. W . , a n d O s g o o d , D . R. D e n ta l a u t o r a d io g r a p h y . I I . E ffe c t o f p r in t in g t e c h n ic s o n in t e r p r e t a tio n . J . D . Res. 36:281 A p r i l 1957. 39. D re iz e n , S., a n d o th e rs. E x p e r im e n t a l o b s e r v a t io n s o n m e la n o id in f o r m a t io n in h u m a n c a r io u s te e th . J . D. Res. 36:233 A p r i l 1957. 40. B hu ssry, B. R., a n d B ib b y , B. G . S u r f a c e In e n a m e l. J . D . Res. 36:409 J u n e 1957.
changes
41. M u r a c c io l e , J . C ., a n d D o m in g u e z , A . T h e p r o d u c t io n o f e x p e r im e n t a l c a r ie s b y s o lu t io n s c o n t a in in g re fin e d c a r b o h y d r a t e s . R e v. A . O d o n t . A r g e n t in a 45:281 A u g . 1957.
C O N G E N IT A L M A L F O R M A T IO N S Samuel Pruzansky, D.D.S., Chicago There are many reasons for the upsurge of interest in congenital malformations; first, because the general problem of causality of congenital malformations in man has become a matter of concern not only to the scientific community but to all who share in responsibility for the conduct of human affairs. This wide spread interest stems from the debate on the genetic effects o f man-made radiation. In 1957, this concern was displayed in newspapers and lay magazines as well as in scientific journals.
There are other reasons, less dramatic but more tangible, that account for the attention given to human malformations. According to a review by Warkany,1 the profile of pediatric practice is changing. With the continued reduction in peri-
A s s o c ia t e p r o f e s s o r o f o r t h o d o n t ic s , S c h o o l o f D e n tistry, U n iv e r s it y o f Illin o is ; a s s o c ia t e d ir e c t o r , c le ft p a la t e c lî n î c t C e n t e r f o r H a n d i c a p p e d C h ild r e n , C h i c a g o P r o fe s s io n a l C o l le g e s , U n iv e r s it y o f Illin o is . I. W a rka n y , a tric s . P e d ia t r ic s
J. C o n g e n i t a l m a lf o r m a t io n s a n d p e d i 19, P a rt 2:725 A p r i l
1957.
634 • T H E J O U R N A L O F T H E A M E R IC A N D EN T A L A S S O C IA T IO N
natal mortality, more attention is focused on every baby death. Congenital malformations now ac count for about 14 per cent of all infant deaths in the United States. In New Zealand, where infant death rates are lower than in the United States, congeni tal malformations at the present time contribute 20 per cent to the general infant mortality. The incidence and importance of con genital malformations cannot be estab lished by mortality statistics alone. Many congenital malformations are undetected until later in life when they are un masked by illness or the development of functional deficits. For example, congeni tal palatal insufficiency is rarely sus pected until the child begins to speak with excessive hypernasality or else the anomaly is unmasked by adenoidectomy.2 The nature o f other congenital malfor mations is such that the child survives only to require continued hospitalization or confinement within the home. In others, successful habilitation as self-sustaining individuals is achieved only as a result of elaborate medical and dental care and special education. For dental science, congenital mal formations of the head offer a challenge and an opportunity.3 The challenge is in the treatment of such patients and the opportunity is in research. These “ experi ments o f nature” on fellow creatures, if properly considered, will yield new and useful knowledge far beyond the patients and the anomalies studied. CASE REPO RTS
As in every other year, the world litera ture contained numerous case reports of human teratomas. In the main, these were o f no special interest for dental science except for reports of cranial defects4 and intraoral5,6 and nasal7,8 dermoid cysts. Pleydell9 reported on an epidemiologi cal study in Northamptonshire of four types of malformations of unknown etiol
ogy— mongolism, congenital malforma tions of the heart, cleft lip and cleft palate, and major malformations of the central nervous system. On the basis of the variable incidence reported from year to year in the same locale, the author sug gested the operation of some inconstant environmental factor such as infection. C ON FEREN CE ON TERATOLOGY
The outstanding publication of the year in the field of teratology was the special supplement to the April 1957 issue of Pediatrics which was devoted to the pro ceedings of a conference on congenital malformation held in Cincinnati, Ohio, in January 1956. At this conference, Patten10 reviewed developmental mechanisms involved in teratogenesis as a basis for a discussion on possible etiologic factors. He pointed out that the concept of “ developmental arrest,” although adequate in explaining cleft lip and cleft palate, failed to ac count for many other defects. Five other mechanisms leading to developmental aberrations were described and the con clusion drawn that it was futile to try to
2. Lis, E. F. The c h ild with c le ft lip a n d c le ft p a la t e . In M a n a g e m e n t o f th e h a n d ic a p p e d c h ild . M ic h a l S m ith , H ., e d it o r . N e w Y o r k , G r u n e & S tra tto n , 1957. 3. P ru zan sk y, S. F o u n d a t io n s o f th e c le ft p a la t e c e n te r a n d t r a in in g p rogra m a t th e U n iv e r s it y o f Illin o is . A n g l e O r t h o d o n t . 27:69 A p r i l 1957. 4. K a p p e r s , J. A . D e v e lo p m e n t a l d is t u r b a n c e o f th e b r a in in d u c e d b y G e r m a n m e a s le s in a n e m b r y o o f th e 7th w e e k . A c t a A n a t . 31:1, 1957. 5. K o t e r la , B. P r z y p a d e k ustne j. ( In t r a - o r a l d e r m o id 12:522 N o v . 1957.
t o r b ie li sk o rz a ste j ja m y c yst.) P o lsk i T y g o d . Lek
6. A le s s i, R. Su un c a s o d i c is ti d e r m o id e g i g a n t e d e l p a v im e n t o d e lla b o c c a ; s t u d io a n a t o m y - t o p o c j r a fic o d e lla r e g io n e s u b lin g u a le , a n a to m o , p a t o l o g ic o e c lin ic o . ( C a s e o f g i a n t d e r m o id c y st o f th e f lo o r o f t h e m o u th ; a n a t o m i c o - t y p o g r a p h ic s t u d y o f th e s u b lin g u a l r e g io n , p a t h o l o g ic a n a to m y and c lin ic a l a s p e c t s . ) M in e r v a C h ir . T o r. 12:308 N o v . 1957. 7. V e rs c h u y l, E.; G r e e p , J . M ., a n d V e r s c h u y l, M . A . A a n g e b o r e n d e r m o id k y s t e n v a n d e n e u s. ( C o n g e n i t a l d e r m o id c ysts o f the n o se .) N e d . T sch r. G e n e e s k . 101:1116 N o v . 1957. 8. F e rra ttI, C . d e r m o id c ysts.) 1957.
E. Q u is t e s d e r m o id e s n a s a le s . ( N a s a l B ol. S o c . d r . U r u g u a y 26:271 N o v .
9. P le y d e ll, M . J . M o n g o l is m _ a n d o th e r a b n o r m a lit ie s : an e p i d e m i o l o g ic a l stu d y h a m p t o n s h ir e . L a n c e t 272:1314 1957.
June
c o n g e n it a l N orth -
in
10. P atten , M . V a r y in g d e v e lo p m e n t a l m e c h a n is m s in t e r a t o lo g y . P e d ia t r ic s 19, P a rt 2:734 A p r i l 1957.
R EV IEW O F 1957 DEN T A L R ESEA R C H . . . V O L U M E 56, M A Y 1958 • 635
find an all-encompassing cause of con genital defects. Patten suggested that de ficiency factors might account for the ‘developmental arrest” type, whereas regulatory factors and disturbances in timing can account for the other cate gories. E X P E R IM E N T A L T E R A T O G E N E S IS
The artificial production of abnormali ties, identical with those arising as the result of gene action, is not only interest ing by virtue of the end result but be comes a useful tool in revealing the mechanisms underlying normal and ab normal processes of development. Pres ent trends in experimental mammalian teratology reveal an expansion of interest from the# morphologic study of abnormal embryos11 and offspring12 for abnormali ties o f physiology13,14 and biochemistry 15,16 l mmunologic phenomena17 and infectious agents18 are also being con sidered. Different teratogenic agents have pro duced artificial counterparts to almost all genetically caused abnormalities. H ow ever, Gluecksohn-Waelsch17 warned that the resemblance of effects produced by different agents, genetic or environ mental, does not necessarily imply actual resemblance of causal mechanisms but rather indicates a resemblance in the function of the reacting system. Thus, the similarity of cortisone-induced and genetically caused cleft palate does not mean that the genetically abnormal in dividual suffers from an excess of corti sone. Instead, it indicates that the mate rial forming the palate is, at a particular stage, susceptible to cortisone as well as to an unknown factor acting on a genetic basis. The question of specificity in experi mental teratology was reviewed by W il son.19 Time-specific effects were demon strated best when minimal effective dosages of various teratogenic agents were used. Agent-specificity was more
difficult to establish from available ex periments because of variability in dosages employed, species studied, age at which the offsprings were examined, and the influence of special interest on the part of the investigator. Nelson20 summarized the information derived from the production of congeni tal anomalies in mammals by maternal dietary deficiencies. The similarity of anomalies resulting from dietary and other teratogenic procedures was strik ing. Acute dietary deficiencies brought on by the use of antimetabolites indicated that the effect usually was limited to the critical period of differentiation and organogenesis, as it is in irradiation. Studies on the inter-relations o f nutri tional and genetic factors were urged as a means of determining individual sus ceptibility to teratogenic conditions. Walker and Fraser21 reported on the embryology of cortisone-induced cleft palate in two strains of mice. They de termined that cortisone treatment caused cleft palate by interfering with the de-
11. M o h a m m e d , C . I. G r o w t h p a t t e r n o f th e rat m a x illa f r o m 16 d a y s in s e m in a t io n a g e to 3 0 d a y s a fte r b ir t h . A m . J. A n a t . 100:115 J a n . 1957. 12. J u lia n , L ; fvj., a n d o th e rs. P r e m a tu r e c lo s u r e of th e s p h e n o - o c c ip it a l s y n c h o n d r o s is in th e h o r n e d H e r e fo rd d w a r f o f th e " s h o r t - h e a d e d " v a r ie t y . A m . J. A n a t . 100:269 M a r c h »957. 13. W o o ll a m , D . H ., a n d M ille n , J . W . E ffe ct o f c o r t is o n e o n t h e in c id e n c e o f c le ft p a la t e in d u c e d b y e x p e r im e n t a l h y p e r v it a m in o s is A . B rit. M e d . J . 5038:197 J u ly 27, 1957. 14. In g a lls , T. H ., a n d C u r le y , F. J . T he re la t io n o f h y d r o c o r t is o n e in j e c t io n s t o c le ft p a la t e in m ic e . N . E n g l a n d J . M . 256:1035 M a y 30, 1957. 15. N e ls o n , M . M ., a n d o th e rs . T e r a t o g e n ic e ffe c ts o f p a n t o t h e n ic a c i d d e f ic ie n c y in th e rat. J . N u t r it io n 62:395 J u l y 1957. 16. M o n ie , I. W . ; N e ls o n , M . M ., a n d E van s, H . M . A b n o r m a l it i e s o f th e u r in a r y sy ste m o f ra t e m b r y o s r e s u lt in g f r o m t r a n s it o r y d e f ic ie n c y o f p t e r o y lg lu t a m ic a c i d d u r i n g g e s t a t io n . A n a t . R e c . 127:711 A p r i l 1957. 17. G lu e c k s o h n - W a e ls c h , S. T r e n d s in m a m m a lia n t e r a t o lo g y . P e d ia t r ic s 19, P a rt 2:7 77 A p r i l 1957. 18. G a b k a , J. T ie r e x p e r im e n t e lle U nte rsu ch u n ge n zu r E r z e u g u n g v o n P h ä n o k o p ie n d u r c h t o x o p la s m e n in fe k t io n . ( E x p e r im e n t a l re s e a r c h o n in d u c t io n o f p h e n o c o p y t h r o u g h t o x o p la s m o s is in fe c t io n .) Z s c h r . m e n sch !. V e r e r b . 34:38 N o v . 1957. 19. W ils o n , J . G . Is th e r e s p e c if ic it y o f a c t io n in e x p e r im e n t a l t e r a t o g e n e s i s ? P e d ia t r ic s 19, P a rt 2:755 A p r i l 1957. 20. N e ls o n , M. M. P r o d u c t io n of c o n g e n it a l a n o m a l ie s in m a m m a ls b y m a t e r n a l d ie t a r y d e f ic ie n c ie s. P e d ia t r ic s 19, P a r t 2:764 A p r i l 1957. 21. W a lk e r , B. E., a n d F ra se r, F. C . T he e m b r y o l o g y o f c o r t is o n e - in d u c e d c le ft p a la t e . J . E m b r y o l. E x p . M o r p h . 5:201 J u n e 1957.
636 • THE J O U R N A L O F THE A M E R IC A N D EN T A L A S S O C IA T IO N
velopment of the condition within the palatine shelves that forces them to change their alignment from the vertical to the horizontal plane. The difference between the two strains in their suscepti bility to the teratogenic action o f corti sone was due in part to the earlier closing o f the palate and lesser inhibition of shelf movement observed in the less susceptible strain of mice. The results of 50 transabdominal amniocenteses in normal human beings during the last two trimesters of preg nancy were reported without evidence of maternal or fetal trauma.22 The contrast to the high incidence of congenital mal formations produced by amniotomy in mice was related to the stage o f preg nancy in which amniocentesis was per formed and the ratio of fetal volume to amniotic fluid in various species. G E N E T IC H A Z A R D S OF R A D IA T IO N
The genetic effects o f radiation on man continued to provoke profound concern among scientists. Crow,23 in theorizing on the mutagenic effects of roentgen rays, gave some crude estimates of the genetic effect to be expected from 10 r of radia tion (the amount recommended as the maximum average gonad dose for the population). Dobzhansky24 wrote, “ as far as genetic effects are concerned, the only safe dose of high-energy radiation is no radiation.” This view was shared by other geneticists.26,26 A recent statement by the United Na tions Scientific Committee on the Effects of Atomic Radiation about the responsi bilities of the medical profession in the use of roentgen rays and other ionizing radiation was a step in the direction of controlling irradiation of human beings.27 An editorial statement28 in t h e j o u r n a l OF
THE
A M E R IC A N
DENTAL
A S S O C IA T IO N
gave reassuring information regarding the minimal gonadal exposure during conventional dental roentgenographic ex amination.
G E N E T IC F A C T O R S
The interaction o f genetic and environ mental factors has been demonstrated on drosophila by Goldschmidt and Piternick,29 and on several strains of mice by Kalter,30 and Fraser and his associates.31 Recently, geneticists have become in terested in American triracial isolates.32 Because of several centuries of in-mar riage, many genetically recessive traits have become manifest and many geneti cally dominant traits have become con centrated in a few families. An excep tionally high incidence of dentinogenesis imperfecta and other hereditary condi tions has been reported in these groups.33 Witkop’s34 survey o f hereditary defects of enamel and dentin in the general popula tion of children allows for interesting comparison with the triracial isolates. Neel35 suggested several useful lines of attack on the genetic aspects o f human teratology. Included were the methods of comparative teratology to determine if
22. P arrish , H . M .; L o c k , F. R., a n d R o u n tre e , M . E. L a c k o f c o n g e n it a l m a lf o r m a t io n s in n o r m a l h u m a n p r e g n a n c ie s a fte r t r a n s a b d o m in a l a m n io c e n t e s is . S c ie n c e 126:77 J u l y 12, 1957. 23. C r o w , J a m e s F. P o s s ib le c o n s e q u e n c e s o f a n in c r e a s e d m u ta tio n rate . E u g e n ic s Q u a r t e r ly 4:67 J u n e 1957. 24. D o b z h a n s k y , T. G e n e t i c lo a d s în t io n s . S c ie n c e 126:191 A u g . 2, 1957. 25. G la s s , B. T h e g e n e t ic h a z a r d s t io n s. S c ie n c e 126:241 A u g . 9, 1957. 26. J a p a n e s e g e n e t ic is t s o n J u ly 12, 1957. 27. U . N . a n d M a r c h 29, 1957.
m e d ic a l
of
n atu ra l
p o p u la
n u c le a r
r a d ia t io n . S c ie n c e
i r r a d ia t io n .
S c ie n c e
ra d ia 126:28 125:592
28. G o n a d a l r a d ia t io n in c id e n t a l t o d e n t a l ro e n t g e n o l o g y a p p e a r s t o b e r e la t iv e ly i n s ig n if ic a n t . J . A . D . A . 55:722 N o v . 1957. 29. G o l d s c h m i d t , R. B., a n d P ite rn ic k , L. K . T he g e n e t ic b a c k g r o u n d o f c h e m ic a l ly in d u c e d p h e n o c o p ie s in d r o s o p h il a . J. Exp. Z o o l . 135:127 J u n e 1957. 30. K a lte r, H . F a c t o r s in f lu e n c in g t h e f r e q u e n c y o f c o r t is o n e - in d u c e d c le ft p a la t e in m ic e . J . E x p . Z o o l. 134:449 A p r i l 1957. 31. F ra se r, F. C . ; W a lk e r , B. E., a n d T ra s le r, D . G . E x p e r im e n t a l p r o d u c t io n o f c o n g e n it a l c le ft p a la t e : g e n e t ic a n d e n v ir o n m e n t a l f a c t o r s . P e d ia t r ic s 19, P a rt 2:782 A p r i l 1957. 32. B eale , C a l v in L. A m e r i c a n t r î- r a c îa l iso la te s: t h e ir sta tu s a n d p e r t in e n c e t o g e n e t ic r e s e a r c h . E u g e n ic s Q u a r t e r ly 4:187 D e c . 1957. 33. W i t k o p , C . J. A s t u d y o f t r i- r a c ia l E a ste rn U n it e d S ta te s. A c t a G e n e t . 6:410,
is o la t e s 1956/7.
in
34. W i t k o p , C . J . H e r e d i t a r y d e f e c t s in e n a m e l a n d d e n t in . A c t a G e n e t . 7:236, 1957. 35. N e e l, J . V. G e n e t ic s a n d h u m a n c o n g e n it a l m a l fo rm a t io n s . P e d ia t r ic s 19, P a r t 2:749 A p r i l 1957.
R EV IEW O F 1957 D EN T A L R ESEA R C H . . . V O L U M E 56, M A Y 1958 • 637
diet and disease are important factors in the statistics of malformations among various peoples; a detailed study of par ents o f affected children, and detailed studies of similarities among siblings with a given defect. Fraser,36 in search of etiologic factors in cleft lip and cleft palate, found that mothers o f such children demonstrated a higher frequency o f pathologic condi tions in the reproductive tract.
C O N C L U S IO N S
The evidence now available stresses the multiplicity and inter-relatedness of etiologic factors as well as the variety of developmental mechanisms involved in the production of congenital malforma tions.
36. F ra se r, F. C . E t i o l o g ic a l f a c t o r s in p a la t e a n d lip . A c t a . G e n e t . 7:229, 1957.
c le fts o f the
R E S E A R C H A N D E D U C A T IO N Paul E. Boyle, D .M .D ., Cleveland Research is concerned with the acquisi tion o f knowledge. Education is the proc ess by which knowledge is passed on to succeeding generations. Volumes have been written on the subject, and it has challenged superior minds from Plato and Aristotle to Whitehead and Hutchins. The primary concern o f this report is the relation of research to education and its bearing on dentistry, including its specialty groups. A brief comment on education in general may be in order before discussing research and the mutual relation of one to the other. In embryology, the statement “ ontogeny recapitulates phylogeny” concisely sum marizes the complex processes o f develop ment. A single cell multiplies, grows, and differentiates, passing through stages reminiscent of ameba, coelenterate, fish and reptile, before finally assuming recog nizable human form. Education is an other complex process through which the squalling infant and the rebellious child become adult, mature members o f so ciety. The momentous changes in the first few weeks of intra-uterine life are more important than anything occurring later in physical development. In much the same way, experiences in infancy and
early childhood are of major significance in the evolution of behavior patterns and emotional characteristics. It is meanipgful to the dental profession that one of the most important instincts of a new born baby is concerned with the mouth. Suckling, contact with the mother and through her with the outside world are functions of a primitive part o f the brain. The sucking reflex is found even in anencephalic monsters. In these formative years the child’s re lation to his mother is paramount. School involves adjustment to a larger circle of adults as well as to others of the same age group. The success with which these ad justments are made depends on the en vironment, the skill o f the teacher and, most of all, on the early experiences of the child. Undue aggressiveness, anxiety, over-dependence, or other behavior prob lems may first manifest themselves at this stage of education, though their roots lie in infancy. The American ideal of equality o f op portunity led to the establishment of public schools. This was a major change from Europe where education was a
D e a n , S c h o o l o f D e n tistry , W e s t e r n R e se rv e U n iv e rs it y .