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Etiology of pre-eclampsia eclampsia
Annotations
Mathematical
physics
One of the facts of life is that in only a few specializations, among them the cardiovascular, is the background of physicians in mathematics and physics totally inadequate; in most of the medical field (general practice, surgery, obstetrics, pediatrics, psychiatry, the greater part of internal medicine, etc.), hardly any or no mathematics at all is needed. The consequence of this is that it is impractical and certainly impossible to adapt the curriculum to the needs of the relatively small group. This is especiallyso since these needs are far greater than is generally realized. The only thing that could be done, anti which has sometunes been tried without success, is to supply the needs of the small group during the time of their specialization. Why did these attempts fail in most cases? Chiefly because the problem of time involved is usually underrated by teachers and students. Because we do not like unpleasant facts, we close our eyes to them. It is an unpleasant fact that nowadays for fruitful research in several medical fields a background in classic physics is needed that is equivalent to that of the well-trained physicist. When the physician cannot acquire this background in a few hours, he is inclined to lose courage and quit. Practically always the teacher has to try to take a shortcut and teach all the necessary mathematics in a very short time by giving a so-called “popular” course, which actually is more a course in mystics than in mathematics. \Ve need not wonder that the only result is a well-cultivated inferiority complex among the students. When the course is
Etiology
of pre-eclampsia
The etiology of specific hypertensive disease of pregnancy has long remained an enigma. Although eclampsia has been recognized as a clinical entit! from antiquity, the primary pathogenetic factor has escaped detection despite extensive clinical study. During the nineteenth century, eclampsia was variously regarded as a form of Bright’s disease, as a primary disease of the iiver, and even as a condition comparable to parturient paresis in cattle. The latter concept led to the practice of mastectomy
710
and the physician
rigorous a11t1 good, the result is nil also, because our medical doctors are not mentally prepared for the amount of self-study and homework that is required. Mq Eh @dwqv &rpanov em yto~e+pra”. “To mathematics there is no path for kings,” and I w:ould like to add, not even for doctors! \2’hen a young doctor wants to specialize and do research work in the cardiovascular lield, he has to be prepared to follow during the first four years of his training three hours of rigorous mathematics and physics lectures per week, lectures that will require from him at least 2 hours of intensive homework per day, weekends not excluded! Hoa this has to be titted into his schedule is his problem and that of the chairman of the department. It is a pity if this problem cannot be solved, for then vvve have to be satisfied to gradually leave more and more of our research to physicists who are willing to spend an equivalent amount of time acquiring knowledge in the cardiovascular field. Teamwork betv,een a physician who knows nothing about physics and a physicist who knows nothing about medicine may seem an attractive substitute, but it does not work. Teamworkers have to understand each other’s language and problems thoroughly. Our young cardiologists have to take the whole dive into the mathematical ocean; just dipping their big toe into the water will irot be sufficient.
eclampsia
as a therapeutic measure, as advocated by Sellheim.6 With the development of a satisfactory practical technique for measurement of blood pressure at the turn of the century, pre-eclampsia was recognized as a hypertensive state preceding the development of convulsions or coma. Subsequently, Volhard,* in 1918, properly emphasized the primary vascular nature of pre-eclampsia eclampsia. However, until recent years a confused state of affairs relative to etiology and diagnosis persisted, as evidenced by
Volume 61 Number 5
Annotations
the inclusion of acute yellow atrophy of the liver, pernicious nausea and vomiting, various renal afflictions, as well as certain hypertensive states peculiar to pregnancy, in the category of “toxemia.” In clinical thinking, the etiological factor common to these various entities was considered to be a toxic material (hence toxemia), a concept culminating in the studies of the Smiths? concerned with the identity of such a substance which presumably was elaborated because of errors in hormone metabolism. A number of authors, including Bastiaanse,’ Brust and co-workers,* Kellar and Sutherland.4 have suggested that a’ pressor substance was responsible for the vascular phenomena basic to the toxemic complex. The possible relation of placental ischemia to the production of a humoral agent has been discussed by Page> but the identity of such a compound or isolation of a pressor material from pregnant animals or the products of conception have been notoriously unsuccessful. However, the recent observations of Hunter and Howard3 indicate that such a pressor material may be consistently isolated from the decidua and amniotic fluid of patients with toxemia, but not from normal pregnant subjects. These findings, if confirmed, may represent a most significant contribution to our understanding of the pathogenesis of acute toxemia of pregnancy. Hunter’s active material has been termed “hysterotonin.” Preliminarv studies supeest that it is a polypeptide of large molecular size, the activity of decidual extracts not being decreased by dialysis. It is lacking in antidiuretic activity and is apparently distinct from angiotonin as well as other polypeptides which produce pressor responses. The active principle is thermostable between pH 3.3 and 8.3 and is rapidly inactivated by kidney extracts, but the pressor activity is potentiated by incubation with plasma. The authors suggest, on the basis of their experimental observations, that hysterotonin is produced by an enzymatic reaction according t3 the following scheme: Enzyme (in decidua) + Protein (in plasma or amniotic fluid) ---f Hysterotonin.
Steroid’
maintenance
711
In consideration of the many disappointments of the theorists over the years concerning the etiology of the specific hypertensive diseases of pregnancy, optimism must be guarded in acceptance of new data bearing on this problem. However, it is hoped that the chemical characterization as well as the kinetics of production of Hunter’s pressor substance will be forthcoming with continued investigation of what may historically be regarded as a major contribution to reproductive research. Richard L. Burt, Winston-Salem,
M.D. N. C.
REFERESCES 1. Bastiaanse, M. A. van B., and Mastboom, J. L.: Ischaemia of the gravid uterus as a probable factor in the causing of toxaemia. Toxaemias of pregnancy, Philadelphia, 1950, Blakiston. 2. Brust, A. A., Assali, N. S., and Ferris, E. B.: Evolution of neurogenic and humoral factors in blood pressure maintenance in normal and toxemia pregnancy, using tetraethylammonium chloride, f. Clin. Invest. 27:717, 1948. .3 . Hunter, C. A., Jr., and Howard, W. F.: A pressor substance’ (hysterotonin) occurring in toxemia, Am. 1. Obst. & Gvnec. 79:838. 1960. 4. Kellar, R. J., ind Sutherland, J. K.: Renin and pregnancy, J. Obst. & Gynaec. Brit. Emp. 48:487, 1941. 5. Page, E. W.: Placental dysfunction in eclamptogenie toxemias, Obst. & Gynec. 5-v. 3:615, 1948. 6. Sellheim, II.: Die mamm&re Theorie iiber die Entstehung des Eklampsiegiftes, Centralbl. f. Gvnnk. 34:1609, 1910. 7. Smith, J. van S.,‘and Smith, 0. W.: Internal secretions and toxemia of late pregnancy, Phvsiol. Rev. 28:l. 1948. 8. Voihard, F. : Die ‘doppelseitigen hematogenen Nierenerkrankungen, Berlin, 1918, Julius Springer.
treatment
in car pulmonale
Although antibiotic therapy has reduced the hazards of acute infection in patients with chronic bronchitis and asthma, it has, by prolonging their lives, encouraged an increased incidence of chronic co1 pulmonale and the prospect of progressive invalidism. Experimental, pathologic, and clinical evidence’-’ indicates that two basic mechanisms, acting alone or in combination, are responsible for this cardiac disability: (1) alveolar hypoventilation with anoxia and hypocapnea inducing pulmonary vasoconstriction, hypervolemia, and increased cardiac out-
put, and (2) anatomic reduction of the pulmonary vasculature. The evidence also suggests that the former is probably the more important mechanism. Thus, acute bronchial infection and emotionally induced asthma, disorders more likely to aggravate anoxia than to accentuate vascular damage, frequently precipitate congestive failure in patients with chronic car pulmonale; and the absence of car pulmonale in patients after pneumonectomy indicates that pulmonary vascular destruction must be extensive before it contributes to the development of this condition. Furthermore, emphysematous
Mathematical
physics
One of the facts of life is that in only a few specializations, among them the cardiovascular, is the background of physicians in mathematics and physics totally inadequate; in most of the medical field (general practice, surgery, obstetrics, pediatrics, psychiatry, the greater part of internal medicine, etc.), hardly any or no mathematics at all is needed. The consequence of this is that it is impractical and certainly impossible to adapt the curriculum to the needs of the relatively small group. This is especiallyso since these needs are far greater than is generally realized. The only thing that could be done, anti which has sometunes been tried without success, is to supply the needs of the small group during the time of their specialization. Why did these attempts fail in most cases? Chiefly because the problem of time involved is usually underrated by teachers and students. Because we do not like unpleasant facts, we close our eyes to them. It is an unpleasant fact that nowadays for fruitful research in several medical fields a background in classic physics is needed that is equivalent to that of the well-trained physicist. When the physician cannot acquire this background in a few hours, he is inclined to lose courage and quit. Practically always the teacher has to try to take a shortcut and teach all the necessary mathematics in a very short time by giving a so-called “popular” course, which actually is more a course in mystics than in mathematics. \Ve need not wonder that the only result is a well-cultivated inferiority complex among the students. When the course is
Etiology
of pre-eclampsia
The etiology of specific hypertensive disease of pregnancy has long remained an enigma. Although eclampsia has been recognized as a clinical entit! from antiquity, the primary pathogenetic factor has escaped detection despite extensive clinical study. During the nineteenth century, eclampsia was variously regarded as a form of Bright’s disease, as a primary disease of the iiver, and even as a condition comparable to parturient paresis in cattle. The latter concept led to the practice of mastectomy
710
and the physician
rigorous a11t1 good, the result is nil also, because our medical doctors are not mentally prepared for the amount of self-study and homework that is required. Mq Eh @dwqv &rpanov em yto~e+pra”. “To mathematics there is no path for kings,” and I w:ould like to add, not even for doctors! \2’hen a young doctor wants to specialize and do research work in the cardiovascular lield, he has to be prepared to follow during the first four years of his training three hours of rigorous mathematics and physics lectures per week, lectures that will require from him at least 2 hours of intensive homework per day, weekends not excluded! Hoa this has to be titted into his schedule is his problem and that of the chairman of the department. It is a pity if this problem cannot be solved, for then vvve have to be satisfied to gradually leave more and more of our research to physicists who are willing to spend an equivalent amount of time acquiring knowledge in the cardiovascular field. Teamwork betv,een a physician who knows nothing about physics and a physicist who knows nothing about medicine may seem an attractive substitute, but it does not work. Teamworkers have to understand each other’s language and problems thoroughly. Our young cardiologists have to take the whole dive into the mathematical ocean; just dipping their big toe into the water will irot be sufficient.
eclampsia
as a therapeutic measure, as advocated by Sellheim.6 With the development of a satisfactory practical technique for measurement of blood pressure at the turn of the century, pre-eclampsia was recognized as a hypertensive state preceding the development of convulsions or coma. Subsequently, Volhard,* in 1918, properly emphasized the primary vascular nature of pre-eclampsia eclampsia. However, until recent years a confused state of affairs relative to etiology and diagnosis persisted, as evidenced by
Volume 61 Number 5
Annotations
the inclusion of acute yellow atrophy of the liver, pernicious nausea and vomiting, various renal afflictions, as well as certain hypertensive states peculiar to pregnancy, in the category of “toxemia.” In clinical thinking, the etiological factor common to these various entities was considered to be a toxic material (hence toxemia), a concept culminating in the studies of the Smiths? concerned with the identity of such a substance which presumably was elaborated because of errors in hormone metabolism. A number of authors, including Bastiaanse,’ Brust and co-workers,* Kellar and Sutherland.4 have suggested that a’ pressor substance was responsible for the vascular phenomena basic to the toxemic complex. The possible relation of placental ischemia to the production of a humoral agent has been discussed by Page> but the identity of such a compound or isolation of a pressor material from pregnant animals or the products of conception have been notoriously unsuccessful. However, the recent observations of Hunter and Howard3 indicate that such a pressor material may be consistently isolated from the decidua and amniotic fluid of patients with toxemia, but not from normal pregnant subjects. These findings, if confirmed, may represent a most significant contribution to our understanding of the pathogenesis of acute toxemia of pregnancy. Hunter’s active material has been termed “hysterotonin.” Preliminarv studies supeest that it is a polypeptide of large molecular size, the activity of decidual extracts not being decreased by dialysis. It is lacking in antidiuretic activity and is apparently distinct from angiotonin as well as other polypeptides which produce pressor responses. The active principle is thermostable between pH 3.3 and 8.3 and is rapidly inactivated by kidney extracts, but the pressor activity is potentiated by incubation with plasma. The authors suggest, on the basis of their experimental observations, that hysterotonin is produced by an enzymatic reaction according t3 the following scheme: Enzyme (in decidua) + Protein (in plasma or amniotic fluid) ---f Hysterotonin.
Steroid’
maintenance
711
In consideration of the many disappointments of the theorists over the years concerning the etiology of the specific hypertensive diseases of pregnancy, optimism must be guarded in acceptance of new data bearing on this problem. However, it is hoped that the chemical characterization as well as the kinetics of production of Hunter’s pressor substance will be forthcoming with continued investigation of what may historically be regarded as a major contribution to reproductive research. Richard L. Burt, Winston-Salem,
M.D. N. C.
REFERESCES 1. Bastiaanse, M. A. van B., and Mastboom, J. L.: Ischaemia of the gravid uterus as a probable factor in the causing of toxaemia. Toxaemias of pregnancy, Philadelphia, 1950, Blakiston. 2. Brust, A. A., Assali, N. S., and Ferris, E. B.: Evolution of neurogenic and humoral factors in blood pressure maintenance in normal and toxemia pregnancy, using tetraethylammonium chloride, f. Clin. Invest. 27:717, 1948. .3 . Hunter, C. A., Jr., and Howard, W. F.: A pressor substance’ (hysterotonin) occurring in toxemia, Am. 1. Obst. & Gvnec. 79:838. 1960. 4. Kellar, R. J., ind Sutherland, J. K.: Renin and pregnancy, J. Obst. & Gynaec. Brit. Emp. 48:487, 1941. 5. Page, E. W.: Placental dysfunction in eclamptogenie toxemias, Obst. & Gynec. 5-v. 3:615, 1948. 6. Sellheim, II.: Die mamm&re Theorie iiber die Entstehung des Eklampsiegiftes, Centralbl. f. Gvnnk. 34:1609, 1910. 7. Smith, J. van S.,‘and Smith, 0. W.: Internal secretions and toxemia of late pregnancy, Phvsiol. Rev. 28:l. 1948. 8. Voihard, F. : Die ‘doppelseitigen hematogenen Nierenerkrankungen, Berlin, 1918, Julius Springer.
treatment
in car pulmonale
Although antibiotic therapy has reduced the hazards of acute infection in patients with chronic bronchitis and asthma, it has, by prolonging their lives, encouraged an increased incidence of chronic co1 pulmonale and the prospect of progressive invalidism. Experimental, pathologic, and clinical evidence’-’ indicates that two basic mechanisms, acting alone or in combination, are responsible for this cardiac disability: (1) alveolar hypoventilation with anoxia and hypocapnea inducing pulmonary vasoconstriction, hypervolemia, and increased cardiac out-
put, and (2) anatomic reduction of the pulmonary vasculature. The evidence also suggests that the former is probably the more important mechanism. Thus, acute bronchial infection and emotionally induced asthma, disorders more likely to aggravate anoxia than to accentuate vascular damage, frequently precipitate congestive failure in patients with chronic car pulmonale; and the absence of car pulmonale in patients after pneumonectomy indicates that pulmonary vascular destruction must be extensive before it contributes to the development of this condition. Furthermore, emphysematous