Reply to Dr. Semchyshyn

Reply to Dr. Semchyshyn

Volume Number Correspondence 139 8 Comments 3180 9 10 3014 8 9 3746 8 9 Primigravid Mexican farmer’s wife, breech, delivered by CS Teacher...

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139 8

Comments 3180









Primigravid Mexican farmer’s wife, breech, delivered by CS Teacher, induced labor, vaginal delivery Nursing instructor, repeat CS












Registered vaginal Housewife, delivery

Nurse, induced delivery induced labor,

that this mode is only suitable tients with good compliance.

for highly

CS labor, vaginal



Stefan Semchyshyn, M.D. Maternal-Fetal Medicine

Obstetrics und Gynecology and Lutheran General Hospital 1775 Dempster Street Park Ridge, Illinois 60068


1. Roversi, G. D., Gargiulo, M., Nicolini, U., et al.: A new approach to the treatment of diabetic pregnant women, AM. J. OBSTET. GYNECOL. 135:567, 1979. 2. Skyler, J. S., Lasky, 1. A., Skyler, D. L., et al.: Home blood glucose monitoring as an aid in diabetes management, Diabetes Care 1:150, 1978. 3. Ikeda, Y., Tajima, N., Minami, N., et al.: Pilot study of self-measurement of blood glucose using the Dextrostix-Eyetone system forjuvenile onset diabetes, Diabetologia 15:91, 1978. 4. Jovanovic, L., Peterson, C. M., Saxena, B. B., et al.: Feasibility of maintaining normal glucose profiles in insulindependent pregnant diabetic women, Am. J. Med. 68:105, 1980. 5. Sonksen, P. H., Judd, S. L., and Lowy, C.: Home monitoring of blood-glucose, Lancet 1:729, 1978. 6. Gonen, B., Rubenstein, A. H., Rochman, H., et al.: Hemoglobin-A1: an indicator of the metabolic control of diabetic patients, Lancet 2:734, 1977. 7. O’Shaughnessy, R., Russ, J., and Zuspan, F. P.: Glyco-

sylated hemoglobins

and diabetes mellitus in pregnancy, 135:783, 1979. 8. Horii, K., Watanabee, G., and Ingalls, T. H.: Experimental AM. J. OBSTET. diabetes


in pregnant


formations in offspring 9. Mills,

J. L., Baker,


of congenital


by insulin, Diabetes 15:194, 1966.

L., and


A. S.: Malformations

in infants of diabetic mothers occur before the seventh gestational week-Implications for treatment, Diabetes 28:292, 1979.

Reply to Dr. Semchyshyn To the Editors:

I would like to thank Dr. Semchyshyn for his observations on my paper which give me the opportunity to revert to the subject.


In 479 pregnant diabetic patients, treated from 1963 to 1975 (682 cases including the years 1976 and 1977), insulin administration at the maximal tolerated dose (MTD) yielded the following results: (1) a reduction in perinatal mortality to values (total, 2.9%; corrected, 1.9%) around the general rate (in 1975, the total perinatal mortality of the general population in the Clinic was 2.5%)‘; (2) virtual disappearance of fetal macrosomia (3.3% above 4,000 gm)’ and normalization of birth weight (newborn weight does not differ from normal newborn weight at the same gestational age)*; (3) a normal incidence of pathologic symptoms in newborn infants, which were not, however, severe (respiratory distress syndrome [RDS], 0.6%; hypoglycemia, 13.4%)2,3; (4) a reduction in cesarean sections to 24.6% (primary, 17.9%)‘; (5) a delivery time that did not have to be systematically brought forward, except in cases where poor condition of the fetus was apparent (labor induced in 9.6% of cases; 74.7% of the patients gave birth after the thirty-eighth week of gestation)‘; (6) the finding that, even though normalization of blood glucose was not the purpose of the treatment, the mean values of fasting and 24-hour (six samples at 4-hour intervals) blood sugar were almost the same in pregnant diabetic patients as in normal pregnant women,2. 4 there being no statistical difference between the two groups; (7) the finding in a recent series of patients treated with insulin at the MTD’ that the psychointellectual development of newborn infants (which is adversely affected in a significant proportion of the offspring of diabetic mothers) was the same as in normal newborn infants. My colleagues and 1 have some difficulty in providing other evidence that would convince Dr. Semchyshyn that “rigid control” of maternal diabetes was achieved in our cases. In any case, “rigid control” is not assured by an “adequate insulin requirement,” but, if anything, by an insulin supply adequate to the insulin requirement. Obviously, these positive results cannot be attributed to our policy of waiting for spontaneous labor, provided that there are no signs of increased risk. However, the reduction of cesarean sections and the virtual disappearance of RDS can definitely be ascribed to this policy. The absence of fetal death in 479 pregnant diabetic women, in 90.4% of whom labor started spontaneously, clearly shows that it is useless to resort systematically to induced labor in pregnant diabetic patients. On the contrary, when induced labor is scheduled in pregnant diabetic patients, the rate of cesarean sections is as much as 60%. We believe that this iatrogenic risk can probably be avoided whenever good compensation of maternal diabetes is reached and fetal well-being can be adequately monitored. We would like to know why Dr. Semchyshyn resorts to induced labor in his cases. Dr. Semchyshyn writes that self-monitoring (and monitoring in general) of blood sugar allows “normal glucose profiles” or “a more physiologic blood concen-



tration” to be achieved and maintained in pregnant diabetic patients. This statement merits a brief comment. It really means that in any given case monitoring of blood sugar helps to reduce hyperglycemia to low values. It does not mean that the blood sugar values obtained correspond to the “normal,” “physiologic” values of that particular case, even if values are reduced to within a normal range (frequently the fear of hypoglycemia results in blood glucose values being lowered to a more risk-free level). The difference may be small or large. As statistical normality is a different matter from individual normality, it would be better to define the blood sugar values to which Dr. Semchyshyn refers as “statistically normal.” This is not without consequence for the fetus. It is clear that fetal risk, especially the major risk, i.e., perinatal death, has been reduced by substantially lowering blood glucose below what was considered optimal up to a few years ago. However, there is still a persistent, high incidence of perinatal abnormality, which shows how far we are from normal or physiologic maternal metabolism. A typical example is fetal macrosomia, which still occurs in 20% to 30% of the case studies in which maternal blood glucose is carefully controlled. In regard to the period of hospitalization, the pregnant diabetic patients in our case study were not selected cases. They included patients of different risks, different degrees of education (even illiterates), etc. 1 believe that in such a population and considering the results, an average period of hospitalization of 51 days may be accepted as positive. Unfortunately, data on this issue are too scarce in the literature to make any comparison. At least 17 of the 5 1 days are necessary to establish the MTD and familiarize the patient with the method. We did not try to reduce the remaining number of days in a highly selected group such as that of Dr. Semchyshyn. As regards intensive monitoring, Dr. Semchyshyn does not take account of the period of our case study, 1963 to 1975. In most of that period, the NST and the OCT were not yet in use as fetal monitoring methods. Following our schedule, fetal monitoring was performed by those methods normally used for managing high-risk pregnancy in the years concerned. Only results can prove the value of any method of fetal monitoring in high-risk pregnancy. It is my opinion that Dr. Semchyshyn underestimates the value of amnioscopy, a simple, virtually cost-free method, which demonstrated its reliability (no prenatal deaths) in our case study. ’ 6 Amniocentesis is a necessary measure when the’interruption of pregnancy is prescribed. When we referred to the teratogenic effects of insulin, we did not mean that insulin has a direct teratogenie effect, which would entail its crossing the placenta. This terminology was used in the sense that high doses of insulin (much higher than those used in therapy) have caused congenital malformations in

April Am. J. Obstet.

15, 1981 Gynecol.

human fetuses; the investigations concerned were quoted. These findings may be summarized as teratogenie effect. Including the case studies of 1976 and 1977, the incidence of total congenital malformations, including those of minor severity such as polysyndactyly, is 2.5% (17/682): Classes A’ and A* (for definition of these classes, see reference 7), 1.8% (6/332); Classes AB, B, and C, 2% (4/201); Classes D, E, and F, 4.7% (7/149). No congenital malformation was observed in 97 newborn infants of patients with gestational (A’, A2) and clinical diabetes without vascular complications compensated in the first trimester of pregnancy, whereas malformations were present in 10 of 436 infants (2.3%) of mothers in the same classes compensated after the first trimester. Congenital malformations in Classes D, E, and F were as follows: first trimester, 9.3% (4/43); after the first trimester, 2.8% (31106); excluding those of minor severity: first trimester, 4.9% (2/41); after the first trimester, 1.9% (2/ 105).* In conclusion, my opinion differs somewhat from that of Dr. Semchyshyn. I agree that perinatal risk in pregnant diabetic patients has been reduced in recent years as a result of the increasing conviction (with some exceptions) that maternal diabetes must be more strictly controlled. Indeed Dr. Semchyshyn’s results are a further confirmation of this. However, I believe, on the grounds of our experience, that perinatal risk can be reduced even further, to the extent that practically risk-free pregnancy can be ensured “a priori.” This requires further investigations. G. D. Rouersi Via E. Besana, 6 20122, Milan, Italy


Roversi, G. D., Gargiulo, M., Nicolini, U., Pedretti, E., Marini, A., Barbarani, V., and Peneff, P.: A new approach to the treatment of diabetic pregnant women. Report of 479 cases seen from 1963 to 1975, AM. J. OBSTET. GYNECOL.

135:567, 1979. G. D., Gargiulo, M., Nicolini, U., Ferrazzi, E., Pe2. Roversi, dretti, E., Gruft, L., and Tronconi, G.: Maximal tolerated insulin therapy in gestational diabetes, Diabetes Care 3:489, 1980. 3. Barbarani, V., Peneff, P., Cattaneo, F., Vitali, 8, and Marini, A.: Les nouveau-n& de mere diabetique dont le diabete fut strictement control& durant la grossesse (resultats cliniaues dans 476 cad. Rev. Med. Suisse Rom. 98:259, 1978 4. Roversi, G. D., Gargiulo, M., Nicolini, U., Pedretti, E., Ferrazzi, E., and Gruft, L.: Normalization of blood glucose in pregnant diabetics with the maximal tolerated dose (MTD) of insulin, J. Perinat. Med. 8: 195, 1980. Guillen, A., ValdPs Amador, A., Duenas Gomez, 5. Marquez E., Valdes Vivo, P., and Mateo de Acosta, 0.: Unsere Erfahrungen mit der prahypoglykimisierenden Insulinbehandlung bei der Betreuung der schwangeren Diabetikerin, Zentralbl. Gynaecol. 100:1481, 1978.

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Roversi, G. D., Canussio, V., Gargiulo, M., Pedretti, E., Nicolini, U., Spreafico, A., Clerici-Bagozzi, D., and Vergani, P.: The importance of amnioscopy in the supervision of the pregnant woman at risk: Retrospective analysis of 4277 cases, J. Perinat. Med. 6~109, 1978. Freinkel, N., and Metzger, B. E.: Pregnancy as a tissue culture experience: the critical implications of maternal metabolism for fetal development, in Pregnancy Metabolism, Diabetes and the Fetus, Ciba Foundation Symposium 63 (new series), Amsterdam, 1979, Excerpta Medica.


venereal neoplasia

To the Editors: I read with great interest the Communication in brief, entitled “Transmissible venereal neoplasia: A case report,” by Dr. Daniel S. Stein (AM. J. OBSTET. GYNECOL. 137:864, 1980). The “unusual association of chronic vulvovaginitis with the subsequent development of vulvar carcinoma in situ in a woman whose husband, 4 years after the untreated lesions were documented in his wife, developed penile carcinoma in situ with focal invasion,” as reported by Dr. Stein, certainly indicates the possibilities of transmissible venereal neoplasia. As to the etiologic agent for the venereal neoplasia, Dr. Stein tended to suggest a viral etiology, based on “the previous reports of vulvar carcinoma in situ associated with documented viral infection and a virusrelated transmissible canine prototype.“’ I have worked on transmission and immunology of the canine transmissible venereal sarcoma for some time and would like to supplement Dr. Stein’s comparative view on the human and canine venereal tumors. Canine transmissible venereal sarcoma (CTVS), also called transmissible tumor of the dog or Sticker’s tumor, is a naturally occurring, contagious neoplasm of dogs which affects the external genitalia of both sexes (Fig. 1). It can be transplanted in nonimmunosuppressed allogeneic dogs with 90% takes in adult dogs and 100% takes in neonatally inoculated puppies.* After a period of rapid growth, the tumor regresses spontaneously in 2 to 6 months in many of the adult dogs but metastasizes in most of the neonatally inoculated puppies.’ The results of cell-free extract transmission studies have been equivocal and a viral etiology of the neoplasm has not been established.” Intact viable cells are needed for successful transmission and the remarkable similarity of karyotypes found in tumors from various parts of the world has led to a stemline lineage hypothesis of the tumor cell transmission.4’ ’ Although virus-like structures have been seen occasionally,‘j attempts at cell-free extract transmission and demonstration of reverse transcriptase have been unsuccessful.’ It is probable that the original tumor was induced by viral or other oncogenic agents centuries ago, but the cell has adapted to grow

Fig. 1. Natural case of canine transmissible venereal sarcoma in a male dog with tumor masses on the glans and prepuce.

in its hosts through rapid passages in nature so that no virus induction is needed for each transmission in the new host. The mechanism of the “universal take” of this tumor which overrides nature’s histocompatibility barrier, is unknown. It is of interest to speculate that had it not been for histocompatibility barriers, there would have been many cases of transmissible venereal neoplasms in man and animals. It would have been of extreme interest had virologic and karyologic studies been done in Dr. Stein’s cases of human transmissible venereal neoplasia. Tsu-Ju (Thomm) Yang, D. V.M., Ph.D. Department of Pathobiology The University of Connecticut Storrs, Connecticut 06268


1. Stein, D. S.: Transmissible venereal neoplasia: A case report, AM.J. OBSTET. GYNECOL. 137:864, 1980. 2. Yang, T. J., and Jones, J. B.: Canine transmissible venereal

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