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ON THE Clinical Classification OF CONGENITAL CARDIAC DISEASE.
164
telephone,
the
wireless) and
of
rapid transport (the the defect
is almost
always
the seat of
strain, and
motor-car, the aeroplane), factors which have so this renders these subjects peculiarly liable to serious materially facilitated the prompt application of complications, especially infective endocarditis or surgical relief in cases of emergency, whether on land endarteritis usually of the subacute bacterial form, or
at
which commonly involves the margins or neighbourhood of the defect, and usually has a lethal termina. tion ; or, in another set of cases, the wall of the aorta may undergo spontaneous rupture, either from a concomitant congenital thinning of its coats, or from increased intra-arterial tension ; or the myocardium itself may fail, leading to cardiac insufficiency or to the conversion of an arterial venous into a venousarterial shunt. The fact that these acyanotic congenital lesions do present a fairly good prognosis in the absence of the grave complications which threaten them, makes their early recognition and the rigid preventive care of such patients imperative. The American Heart Association classifies patients with healed rheumatic lesions as " potential cardiacs," and prescribes for these the removal of foci of infection, proper rest, and careful supervision with a view to the avoidance of undue strain, and the elimination It is surely desirable that of unnecessary risks. acyanotic congenital cardiacs should be similarly classified, and as carefully safeguarded and watched.
sea.
I trust, however, that enough has been said to indicate that modern surgery, with the aid of its allies, has made, and is still making, great progress towards that end we all so fervently desire-the prevention of those abnormal conditions, the late results of which to-day necessitate so much surgical attention of a destructive rather than a constructive character. Much yet remains to be done, and the natural sciences must continue to advance, each ready to assist and to accept assistance from its fellows, each along its own special path yet all in mutual friendly alliance working for the common good, all in zealous pursuit of that goal, unattainable though it must ever remain, that will-o’-the-wisp of perfect knowledge and complete understanding. In so doing they will but follow the precept and the spirit of that motto upon the crest of our beloved University, in whose venerable precincts this great Association will to-morrow enter upon its full scientific programme, and of which we in this city are all so intensely proud; "Arduus ad solem "-"leaping upwards to the sunshine "-‘ever striving towards the very highest."
ON
THE
Clinical Classification OF
CONGENITAL CARDIAC DISEASE.* BY MAUDE E.
ABBOTT, M.D. MCGILL.,
ASSISTANT PROFESSOR OF MEDICAL RESEARCH, MCGILL
UNIVERSITY,
MONTREAL.
CLINICIANS do not always recognise the fact that oongenital cardiac disease does not necessarily mean " blue baby " or morbus caeruleus, with its familiar symptom-complex of cyanosis, dyspnoea, and clubbing, and its progressively downward course. This condition gives little scope for the physician’s skill, since the deficient oxygenation of the blood thus revealed is the result of unalterable structural changes in the heart. On the other hand, there exists a larger and clinically a much more important group of congenital cardiac patients to whom the word " acyanotic " applies, for the reason that these patients do not, under otherwise normal conditions in the body, present any raised oxygen-unsaturation at all, so that they show either no cyanosis, or cyanosis only as a transient or very " late " phenomenon. In this group are included those congenital lesions in which
DIAGNOSIS.
I
congenital cardiac lesion of the acyanotic group may usually be " picked up " by detecting, in an otherwise apparently normal individual, the presence of pulsation murmur or thrill of unusual localisation A
and character in the cardiovascular area. Incidentally, these people often display the slender habitus characteristic of the hypoplasia of the aorta often associated with this congenital lesion. With the help of X rays a further differential diagnosis can often be made between such classic conditions as coarctation of the aorta, subaortic stenosis, and the various forms of cardiovascular septal defects (patent ductus, maladie de Roger, and so forth). In infants under one year, however, practically no differentiation into " cyanotic " or " acyanotic" types can be made with certainty because, excepting the most complex cases of extreme morbus cseruleus. cyanosis often does not manifest itself until after many months of postnatal life. So that one must here be content as a rule with the mere recognition of the presence of a congenital lesion, until sufficient time has elapsed after birth for the manifestation of cyanosis after the " threshold-value " of raised oxygen-unsaturation is reached.
THE CYANOTIC GROUP. A word may be added regarding the diagnosis of the cyanotic group, though this is of much less practical importance. Once infancy is past, these subjects are readily recognised by their very striking symptomatology, especially the cyanotic hue, which deepens on exercise ; and when to these appearances are added atypical physical signs over the cardiac area no abnormal communication between the two circu- the presence of a morbus cseruleus is readily establations exists, so that venous blood does not enter lished. Differentiation of the exact lesion present in the arterial stream as a result of the anomaly- such a cyanotic case can scarcely be determined with e.g., coarctation of the aorta-and also the localised certainty, but only a few combinations survive into cardiovascular septal defects, in which, in the absence adult life (see classification below), and of these that of complications and under the physiological conditions most commonly met with in cyanotic patients reaching of relatively higher pressure in the systemic circula- early adult life is the " tetralogy of Fallot " (pultion, blood passes from left to right through the defect. monary stenosis, with associated ventricular septal In these cases an arterial-venous shunt exists, which defect and dextroposition of the aorta). These may, in the event of a pathological rise of pressure in conditions exist in at least 75 per cent. of cyanotic the right chambers, be temporarily converted into a young adults with congenital lesions. In cyanotic venous-arterial shunt, with the appearance of transient patients living beyond middle life one may suspect or terminal cyanosis. complete defect of the interventricular septum (cortriloculare biatriatrium) or pulmonary stenosis with ACYANOTIC CASES. interventricular septum, since statistics show closed " These so-called acyanotic " cases are of great that the average duration of life in these cases is importance to the clinician, for such patients have relatively long. a relatively good expectation of life, and may live to an advanced age without showing any sign of being CLINICAL CLASSIFICATION. hampered by their anomaly. On the other hand, Under the classification set out below, which I have elaborated in the section on Congenital Cardiac * Abridged from an address delivered at the New Sussex Disease in the third edition of Osler and Macrae’s Hospital, Brighton, on July 20th, 1929.
165 " Modern Medicine " (London, 1927), the principal of aorta with defect at base of ventricular septum ; cardiac anomalies are grouped in the order of their complete absence of ventricular septum (cor biatriatrium triloculare) ; pulmonary stenosis of inflammatory type clinical importance. with closed ventricular septum and patent foramen ovale ; A. OF CLINICAL SIGNIFICANCE. tricuspid atresia with interauricular septal defect and transposition of the great trunks. (b) Marked cyanosis: : PulI. Non-cyanotic Group. monary stenosis with dextroposition of aorta and inter1. Cases in which no abnormal communication exists, but ventricular septal defect (tetralogy of Fallot) ; pulmonary in which the defect may produce a mechanical interference atresia with ventricular septal defect, dextroposition of the with the circulation which become the seat of strain. aorta, and patent ductus ; transposition of arterial trunks These are : pericardial defect; ectopia cordis abdominalis ; with ventricular septal defects and dextroposition of the primary congenital hypertrophy ; congenital heart-block ; I aorta. Complete absence of (e) Extreme eyanosis: anomalous septa ; pulmonary and tricuspid insufficiency ; cardiac septa (cor biloculare) ; complete defect of aortic aortic and mitral stenosis ; anomalies of semilunar and septum (persistent truncus) ; transposition of arterial trunks auriculo-ventricular cusps ; coarctation and hypoplasia of with patent foramen ovale and patent ductus but closed the aorta; anomalies of the aortic arch; anomalies of interventricular septum: pulmonary atresia with closed coronary arteries ; congenital arteriovenous aneurysm; ventricular septum, patent foramen ovale and patent certain anomalies of veins and anomalies of pulmonary ductus ; aortic and mitral atresia with defect of interartery. ventricular septum and aplasia of aorta. 2. Cases of arterial-venous shunt with terminal
possible
transient reversal of flow (cyanose tardive): (a) Defects of the interauricular septum (persistent ostium primum ; persistent ostium secundum ; patent foramen ovale ; multiple defects ;; complete defect (cor-biventriculare triloculare). (b) Localised defects at the base of the interventricular septum (Maladie de Roger; defects below; multiple). (c) Patent ductus arteriosus and localised defects of aortic septum (communication just above the aortic valve ; congenital aneurysm of the right aortic sinus of Valsalva). or
II. Cyanotic Group. (Morbus eceruleus.) 1. Cases of venous-arterial shunt (arranged in order of severity of shunt). (a) Moderate cyanosisDextroposition .
2. Cases of Raised Peripheral Pressure. Riqht-8ided valvular lesions with closed septa (pulmonary and tricuspid
stenosis).). B. CASES OF No CLINICAL SIGNIFICANCE. Diverticulum of pericardium; bifid apex of heart ; diverticulum of heart ; acardia, ectopia cordis pectoralis (non-viable) ; congenital rhabdomyoma ; true (mirrorpicture) dextrocardia.
[Dr. Abbott demonstrated with the the different defects, and
diagrams illustrating
an
epidiascope
of the circulation in photographs of the corre-
course
sponding pathological specimens.] a
basis of
glycerinated extract
of
potato (1907).
THE BACTERIOLOGICAL DIAGNOSIS OF Even on this special medium their organism grew remarkably slowly, two-three days elapsing before WHOOPING-COUGH.
colonies appeared. In the examination of specimens of sputum from patients who had been affected with whooping-cough for some time, Bordet AND and Gengou found in almost every case and apart J. W. McLEOD, M.B. GLASG., from the B. pertussis, an organism identical with BROTHERTON PROFESSOR OF BACTERIOLOGY IN THE UNIVERSITY or very similar to the bacillus found by Pfeiffer in OF LEEDS. It was, however, smaller than cases of influenza. B. pertussis and it showed a marked tendency to SINCE the original work of Bordet and Gengou pleomorphism and to the development of involution (1906), in which they demonstrated the existence forms. Bordet and Gengou also showed that this of a bacillus morphologically similar to, but distinct organism was met quite frequently in other respiratory In a series of from the influenza bacillus, in the sputum of patients affections besides whooping-cough. suffering from whooping-cough, there has been very papers published subsequently Bordet elaborated little attempt, except in Denmark, to make a practical and confirmed his original observations with Gengou application of these findings. The medical profession on the morphological and cultural characters of has not resorted to the bacteriological diagnosis of the B. pertussis found by them in early cases of The reasons for this i whooping-cough (1907, 1908, 1909 and 1912).. doubtful whooping-cough. Kristensen (1922) has drawn attention to two may be that a certain scepticism still prevails about If the aetiological connexion of the bacillus which additional points of contrast between these bacilli: these observers described with this disease and that (1) the capacity of B. pertussis to survive for considerit has not been realised that the differentiation of able periods on suitable media at low temperature, this bacillus from the influenza bacillus is easily a character lacking in B. influenzae in his observations, and (2), more important still, the inability of made. Observations such as those of Wollstein (1909) B. pertussis to grow freely on the media best adapted and Scheller (1912), who found difficulty in repeating for the growth of B. influenzce, such as Levinthal’s, Convinced by these and other Bordet’s serological observations in the disease, chocolate agar," &c. have probably contributed to this scepticism, and points of the ease. with which B. pertussis can be many of the statements in the text-books and else- differentiated from B. influenzce, the staff of the where leave the impression that the differentiation Danish State Serum Institute has been carrying on the between B. influenzce and B. pertussis rests on some bacteriological diagnosis of whooping-cough for several relatively fine points-e.g., Andrewes (1920), in years for the benefit of general practitioners and discussing the influenza group of bacteria, says, others. So far as we are aware no attempt has been made " Many bacteriologists would agree that we may be confounding under the common term, B. influenza, to corroborate or reject Bordet and Gengou’s findings a number of closely related species. Bordet’s in this country. At all events, we have been unable ’ whooping-cough bacillus’ would fall into such to find any record of it. It is not clear from the a group." published records whether Freeman’s work relates It is one of the purposes of this paper to emphasise entirely to observations made with cultures obtained afresh the facts already indicated by Bordet and more from Bordet or refers also to strains isolated by recently stressed by Kristensen (1922) that although himself (1909). In view of this state of affairs it these bacilli are probably related species there is seemed desirable to find how far the results obtained little ground beyond that of microscopic morphology in Belgium and Denmark could be corroborated for confusing them. In the examination of the thick in this country ; and in case they should be, to control whitish exudate expectorated in the early stages the observations by determining the frequency of the disease, Bordet and Gengou demonstrated the with which this bacillus could be detected in the presence of a small Gram-negative ovoid microbe, trachea and bronchi of children dying from various constant in size and appearance (1906). The medium causes other than whooping-cough. The last type used for successful cultivation was blood-agar with of observations does not appear to have been made the
BY H.
SUGARE, M.D. LEEDS,
"
-
I
telephone,
the
wireless) and
of
rapid transport (the the defect
is almost
always
the seat of
strain, and
motor-car, the aeroplane), factors which have so this renders these subjects peculiarly liable to serious materially facilitated the prompt application of complications, especially infective endocarditis or surgical relief in cases of emergency, whether on land endarteritis usually of the subacute bacterial form, or
at
which commonly involves the margins or neighbourhood of the defect, and usually has a lethal termina. tion ; or, in another set of cases, the wall of the aorta may undergo spontaneous rupture, either from a concomitant congenital thinning of its coats, or from increased intra-arterial tension ; or the myocardium itself may fail, leading to cardiac insufficiency or to the conversion of an arterial venous into a venousarterial shunt. The fact that these acyanotic congenital lesions do present a fairly good prognosis in the absence of the grave complications which threaten them, makes their early recognition and the rigid preventive care of such patients imperative. The American Heart Association classifies patients with healed rheumatic lesions as " potential cardiacs," and prescribes for these the removal of foci of infection, proper rest, and careful supervision with a view to the avoidance of undue strain, and the elimination It is surely desirable that of unnecessary risks. acyanotic congenital cardiacs should be similarly classified, and as carefully safeguarded and watched.
sea.
I trust, however, that enough has been said to indicate that modern surgery, with the aid of its allies, has made, and is still making, great progress towards that end we all so fervently desire-the prevention of those abnormal conditions, the late results of which to-day necessitate so much surgical attention of a destructive rather than a constructive character. Much yet remains to be done, and the natural sciences must continue to advance, each ready to assist and to accept assistance from its fellows, each along its own special path yet all in mutual friendly alliance working for the common good, all in zealous pursuit of that goal, unattainable though it must ever remain, that will-o’-the-wisp of perfect knowledge and complete understanding. In so doing they will but follow the precept and the spirit of that motto upon the crest of our beloved University, in whose venerable precincts this great Association will to-morrow enter upon its full scientific programme, and of which we in this city are all so intensely proud; "Arduus ad solem "-"leaping upwards to the sunshine "-‘ever striving towards the very highest."
ON
THE
Clinical Classification OF
CONGENITAL CARDIAC DISEASE.* BY MAUDE E.
ABBOTT, M.D. MCGILL.,
ASSISTANT PROFESSOR OF MEDICAL RESEARCH, MCGILL
UNIVERSITY,
MONTREAL.
CLINICIANS do not always recognise the fact that oongenital cardiac disease does not necessarily mean " blue baby " or morbus caeruleus, with its familiar symptom-complex of cyanosis, dyspnoea, and clubbing, and its progressively downward course. This condition gives little scope for the physician’s skill, since the deficient oxygenation of the blood thus revealed is the result of unalterable structural changes in the heart. On the other hand, there exists a larger and clinically a much more important group of congenital cardiac patients to whom the word " acyanotic " applies, for the reason that these patients do not, under otherwise normal conditions in the body, present any raised oxygen-unsaturation at all, so that they show either no cyanosis, or cyanosis only as a transient or very " late " phenomenon. In this group are included those congenital lesions in which
DIAGNOSIS.
I
congenital cardiac lesion of the acyanotic group may usually be " picked up " by detecting, in an otherwise apparently normal individual, the presence of pulsation murmur or thrill of unusual localisation A
and character in the cardiovascular area. Incidentally, these people often display the slender habitus characteristic of the hypoplasia of the aorta often associated with this congenital lesion. With the help of X rays a further differential diagnosis can often be made between such classic conditions as coarctation of the aorta, subaortic stenosis, and the various forms of cardiovascular septal defects (patent ductus, maladie de Roger, and so forth). In infants under one year, however, practically no differentiation into " cyanotic " or " acyanotic" types can be made with certainty because, excepting the most complex cases of extreme morbus cseruleus. cyanosis often does not manifest itself until after many months of postnatal life. So that one must here be content as a rule with the mere recognition of the presence of a congenital lesion, until sufficient time has elapsed after birth for the manifestation of cyanosis after the " threshold-value " of raised oxygen-unsaturation is reached.
THE CYANOTIC GROUP. A word may be added regarding the diagnosis of the cyanotic group, though this is of much less practical importance. Once infancy is past, these subjects are readily recognised by their very striking symptomatology, especially the cyanotic hue, which deepens on exercise ; and when to these appearances are added atypical physical signs over the cardiac area no abnormal communication between the two circu- the presence of a morbus cseruleus is readily establations exists, so that venous blood does not enter lished. Differentiation of the exact lesion present in the arterial stream as a result of the anomaly- such a cyanotic case can scarcely be determined with e.g., coarctation of the aorta-and also the localised certainty, but only a few combinations survive into cardiovascular septal defects, in which, in the absence adult life (see classification below), and of these that of complications and under the physiological conditions most commonly met with in cyanotic patients reaching of relatively higher pressure in the systemic circula- early adult life is the " tetralogy of Fallot " (pultion, blood passes from left to right through the defect. monary stenosis, with associated ventricular septal In these cases an arterial-venous shunt exists, which defect and dextroposition of the aorta). These may, in the event of a pathological rise of pressure in conditions exist in at least 75 per cent. of cyanotic the right chambers, be temporarily converted into a young adults with congenital lesions. In cyanotic venous-arterial shunt, with the appearance of transient patients living beyond middle life one may suspect or terminal cyanosis. complete defect of the interventricular septum (cortriloculare biatriatrium) or pulmonary stenosis with ACYANOTIC CASES. interventricular septum, since statistics show closed " These so-called acyanotic " cases are of great that the average duration of life in these cases is importance to the clinician, for such patients have relatively long. a relatively good expectation of life, and may live to an advanced age without showing any sign of being CLINICAL CLASSIFICATION. hampered by their anomaly. On the other hand, Under the classification set out below, which I have elaborated in the section on Congenital Cardiac * Abridged from an address delivered at the New Sussex Disease in the third edition of Osler and Macrae’s Hospital, Brighton, on July 20th, 1929.
165 " Modern Medicine " (London, 1927), the principal of aorta with defect at base of ventricular septum ; cardiac anomalies are grouped in the order of their complete absence of ventricular septum (cor biatriatrium triloculare) ; pulmonary stenosis of inflammatory type clinical importance. with closed ventricular septum and patent foramen ovale ; A. OF CLINICAL SIGNIFICANCE. tricuspid atresia with interauricular septal defect and transposition of the great trunks. (b) Marked cyanosis: : PulI. Non-cyanotic Group. monary stenosis with dextroposition of aorta and inter1. Cases in which no abnormal communication exists, but ventricular septal defect (tetralogy of Fallot) ; pulmonary in which the defect may produce a mechanical interference atresia with ventricular septal defect, dextroposition of the with the circulation which become the seat of strain. aorta, and patent ductus ; transposition of arterial trunks These are : pericardial defect; ectopia cordis abdominalis ; with ventricular septal defects and dextroposition of the primary congenital hypertrophy ; congenital heart-block ; I aorta. Complete absence of (e) Extreme eyanosis: anomalous septa ; pulmonary and tricuspid insufficiency ; cardiac septa (cor biloculare) ; complete defect of aortic aortic and mitral stenosis ; anomalies of semilunar and septum (persistent truncus) ; transposition of arterial trunks auriculo-ventricular cusps ; coarctation and hypoplasia of with patent foramen ovale and patent ductus but closed the aorta; anomalies of the aortic arch; anomalies of interventricular septum: pulmonary atresia with closed coronary arteries ; congenital arteriovenous aneurysm; ventricular septum, patent foramen ovale and patent certain anomalies of veins and anomalies of pulmonary ductus ; aortic and mitral atresia with defect of interartery. ventricular septum and aplasia of aorta. 2. Cases of arterial-venous shunt with terminal
possible
transient reversal of flow (cyanose tardive): (a) Defects of the interauricular septum (persistent ostium primum ; persistent ostium secundum ; patent foramen ovale ; multiple defects ;; complete defect (cor-biventriculare triloculare). (b) Localised defects at the base of the interventricular septum (Maladie de Roger; defects below; multiple). (c) Patent ductus arteriosus and localised defects of aortic septum (communication just above the aortic valve ; congenital aneurysm of the right aortic sinus of Valsalva). or
II. Cyanotic Group. (Morbus eceruleus.) 1. Cases of venous-arterial shunt (arranged in order of severity of shunt). (a) Moderate cyanosisDextroposition .
2. Cases of Raised Peripheral Pressure. Riqht-8ided valvular lesions with closed septa (pulmonary and tricuspid
stenosis).). B. CASES OF No CLINICAL SIGNIFICANCE. Diverticulum of pericardium; bifid apex of heart ; diverticulum of heart ; acardia, ectopia cordis pectoralis (non-viable) ; congenital rhabdomyoma ; true (mirrorpicture) dextrocardia.
[Dr. Abbott demonstrated with the the different defects, and
diagrams illustrating
an
epidiascope
of the circulation in photographs of the corre-
course
sponding pathological specimens.] a
basis of
glycerinated extract
of
potato (1907).
THE BACTERIOLOGICAL DIAGNOSIS OF Even on this special medium their organism grew remarkably slowly, two-three days elapsing before WHOOPING-COUGH.
colonies appeared. In the examination of specimens of sputum from patients who had been affected with whooping-cough for some time, Bordet AND and Gengou found in almost every case and apart J. W. McLEOD, M.B. GLASG., from the B. pertussis, an organism identical with BROTHERTON PROFESSOR OF BACTERIOLOGY IN THE UNIVERSITY or very similar to the bacillus found by Pfeiffer in OF LEEDS. It was, however, smaller than cases of influenza. B. pertussis and it showed a marked tendency to SINCE the original work of Bordet and Gengou pleomorphism and to the development of involution (1906), in which they demonstrated the existence forms. Bordet and Gengou also showed that this of a bacillus morphologically similar to, but distinct organism was met quite frequently in other respiratory In a series of from the influenza bacillus, in the sputum of patients affections besides whooping-cough. suffering from whooping-cough, there has been very papers published subsequently Bordet elaborated little attempt, except in Denmark, to make a practical and confirmed his original observations with Gengou application of these findings. The medical profession on the morphological and cultural characters of has not resorted to the bacteriological diagnosis of the B. pertussis found by them in early cases of The reasons for this i whooping-cough (1907, 1908, 1909 and 1912).. doubtful whooping-cough. Kristensen (1922) has drawn attention to two may be that a certain scepticism still prevails about If the aetiological connexion of the bacillus which additional points of contrast between these bacilli: these observers described with this disease and that (1) the capacity of B. pertussis to survive for considerit has not been realised that the differentiation of able periods on suitable media at low temperature, this bacillus from the influenza bacillus is easily a character lacking in B. influenzae in his observations, and (2), more important still, the inability of made. Observations such as those of Wollstein (1909) B. pertussis to grow freely on the media best adapted and Scheller (1912), who found difficulty in repeating for the growth of B. influenzce, such as Levinthal’s, Convinced by these and other Bordet’s serological observations in the disease, chocolate agar," &c. have probably contributed to this scepticism, and points of the ease. with which B. pertussis can be many of the statements in the text-books and else- differentiated from B. influenzce, the staff of the where leave the impression that the differentiation Danish State Serum Institute has been carrying on the between B. influenzce and B. pertussis rests on some bacteriological diagnosis of whooping-cough for several relatively fine points-e.g., Andrewes (1920), in years for the benefit of general practitioners and discussing the influenza group of bacteria, says, others. So far as we are aware no attempt has been made " Many bacteriologists would agree that we may be confounding under the common term, B. influenza, to corroborate or reject Bordet and Gengou’s findings a number of closely related species. Bordet’s in this country. At all events, we have been unable ’ whooping-cough bacillus’ would fall into such to find any record of it. It is not clear from the a group." published records whether Freeman’s work relates It is one of the purposes of this paper to emphasise entirely to observations made with cultures obtained afresh the facts already indicated by Bordet and more from Bordet or refers also to strains isolated by recently stressed by Kristensen (1922) that although himself (1909). In view of this state of affairs it these bacilli are probably related species there is seemed desirable to find how far the results obtained little ground beyond that of microscopic morphology in Belgium and Denmark could be corroborated for confusing them. In the examination of the thick in this country ; and in case they should be, to control whitish exudate expectorated in the early stages the observations by determining the frequency of the disease, Bordet and Gengou demonstrated the with which this bacillus could be detected in the presence of a small Gram-negative ovoid microbe, trachea and bronchi of children dying from various constant in size and appearance (1906). The medium causes other than whooping-cough. The last type used for successful cultivation was blood-agar with of observations does not appear to have been made the
BY H.
SUGARE, M.D. LEEDS,
"
-
I