- Email: [email protected]
Drug induced teratogenesis
Volume 88 :\lumber 4
*Grant, M. P. S.: Cytology in Prevention of Cancer of Cervix, p. 1637. MacGregor and Baird: Detection of Cervical Carcinoma in the General Population, p. 1631. A screening program for cervical carcinoma in Aberdeen during 1961 yielded 8,010 smears. Smears were obtained from parous women between the ages of 25 and 60 who were hospitalized on general hospital wards and from married women of the same age group who were under the care of three family physicians. Eighteen cases of clinically unsuspected preinvasive or early invasive carcinoma were detected. In data collected in Aberdeen, among women in the 25 to 60 age group, the mean age at the time of the diagnosis of a preinvasive cervical lesion was 39.6 years, of an invasive lesion, 43.6 years, and of a clinically detectable lesion, 48.3 years. On the basis of these figures, the authors suggest that rescreening of individuals be carried out at intervals of 5 years. The cost of diagnosing one case of cervical carcinoma under such a program is calculated to amount to 59 pounds. The cases of cervical carcinoma detected by the screening technique were by and large in women of high parity, who were in a low socioeconomic group. Since these women are the least likely to respond to invitations to appear for screening smears, the family physician's position is stressed in encouraging cytologic detection among his patients. Edward E. Wallach
Grant: Cytology in Prevention of Cancer of Cervix, p. 1637. The results of a study of cervical cytology in a group of 3,366 patients is presented. The group included 35 patients with clinically obvious cervical carcinoma and 275 patients clinically suspected of having cervical cancer. Five carcinomas were detected in the latter group. In the remaining patients there were 35 unsuspected cervical malignancies ( 1.04 per cent incidence). In all there were 75 malignant lesions. The average age of the 31 patients with in situ carcinoma was 40.0 years and of the 44 patients with invasive carcinoma, 55.5 years. High parity in this series did not appear to have an influence on the development of cervical carcinoma. Unsuspected cancers were found equally in patients with cervical erosions and in those without erosions. The 15.5 year difference in the mean age of the patients in the in situ cancer and invasive cancer groups
Selected abstracts 563
supports the view that m situ carcinoma progresses to invasiveness. Edward E. Wallach
Canadian Medical Association Journal Vol. 87, No. 12. *Ives, E.: Thalidomide and Anal Abnormalities, p. 670. lves: Thalidomide and Anal Abnormalities, p. 670. Two cases of severe anal stenosis in newborn infants are reported. Each mother had been given thalidomide between the third and eighth weeks of gestation. In one case the exact amount and time of administration was known. The embryology of the anus is reviewed, and it is postulated that the patients received the teratogenic agent after the formation of the limbs and during the canalization of the anal canal. A need for vigorous testing of drugs given to pregnant patients is urged.
Harvey Cohen No. 13. *Frazer, F. C.: Drug Induced Teratogenesis, p. 683. *Ringrose, C. A. D.: The Obstetrical Use of Ergot: A Violation of the Doctrine "Primum Non Nocere," p. 712. Frazer: Drug Induced Teratogenesis, p. 683. The author relates certain principles established in experimental teratology to the problem of teratogenesis in the human. Each teratogen is thought to produce its re· suits by specific pharmacological action on par· ticular embryonic tissues. The malformation pro· duced depends upon the agent, the dose, the spe· cies, the genetic constitution of both the mother and the embryo, and the stage of development. Attention is called to certain drugs given prenatally which have adverse postnatal effects such as some hypertensive agents that produce hypertension in the offspring of rats. A summation effect of two teratogens which individually do not produce malformations, but which together do, is discussed. A list of teratogenic drugs in animals is presented, as well as those suspected or known in humans. Trials of therapy, from implantation to term, of new drugs in experimental animals would be beneficial, in that possible dangers could be uncovered which may also be present in humans. The author stresses the need of a program
564
Selected abstracts
whereby all drugs given to pregnant women are recorded and the infants arc examined for possible harmful effects. No medication not definitely indicated should be administered tn pregnant women. Harvey Cohen
Ringrose: Obstetrical Use of Ergot: Violation of the Doctrine "Primum Non Nocere," p. i!2. The death of a 17-year-old primigravida, attributed to the use of intravenous ergonovinP maleate, 0.2 mg., is presented. The patient had a normal prenatal course; labor and delivery ·were spontaneously facilitated by a pudendal block of I per cent lidocaine, without any vascoconstrictor drug and episiotomy. The oxytocic agent was given with the crowning of the hPad following which the patient became nauseated, retched, and developed hypertmsion which pe-rsisted for 90 minutes. Because of a persistent heaclach(' a spinal tap was clone on the second postpartum clay which revealed bloody spinal fluid. Bilateral carotid angiograms were normal. The patient became semicomatose following the angiograms and shP died on the seventh postpartum clay. Postmortem examination revealed an intracerebral hemorrhage in the right frontal lobe rupturing into the subarachnoid space and right lateral ventricle. Any evidence of pre-existing lesions was obscured by hemorrhagP. The author attributes the death to th(· use of the ergot preparation. The role of ergot preparations in obstetrics is discussed. The use of oxytocic agents devoid of pressor pffects is advocated, as well as questioning the nf'ed of ergot derivatives and their prophylactic usc. Han'C}' Cohen No. 24 *Taylor, W. C.: Mortality and Morbidity of Exchange Transfusion, p. 1267.
Feb1 ua1 y 1:'1,
.-\m.
J.
1'!6-1
Ob>t. & Gvnec.
Taylor: Mortality and Morbidity of Exchange Transfusion, p. 1267. A study to ascertain both the morbidity and the mortality rates from exchange transfusions with citrated donor blood is presented. One hundred and four cases of infants requiring 150 exchange transfusions were reviewed. Seventy-two infants had Rh hemolytic disease, 22 had ABO hemolytic disease, and in I 0 the f'tiology was not ascrrtainecl. In 44 infants, representing ti2 exchange transfusions, electrocarcliograrns and biochemical determinations were performed. The-n· \Vf'rf' 8 total deaths. 3 of \\'hich \\·ere not considered to be n·latecl to the proceclurr. The rrmaining 5 deaths, representing a 4.8 per c••nt infant death rate are summarized. One death was directly related to the procedure of exchange transfusion, and in the othPr +, the proc('cltlff' was considered to be partly responsible for the death. Otht'r factors involved were anemia with a h\'moglobin of less than 10 Gm., prematurity, and hyperpotasscmia. In th(' ti2 transfusions, during which investigativt· procedures were performed, clinically recognizabiP disturbances wne present in 3 7 per cent. ThP majority of disturbances werr vomiting and n·tching·, 23 pPr cent; respiratory distress, 10 per cent; and convulsions or tf'tany, 8 per cent. The ratP of injPction influenced the incidence of retching and \·omiting, and thP author states that a (k~irable ratt· is 2 mi. per kilogram per rninutc. ThP hazard with tht· use of citratrcl donor blood is clisntssPcl and the use of donor blood rnorf' than 5 claYs old is conclemnccl because of , • ,..... "• uw mgn lt'\Wl orr porassmm. vonvulsions and• tetany art' prcwntecl if 1 mi. of I 0 per cent calcium gluconate is injected after each I 00 cr. of blood has been exchanged. .I
I
•
I
1
1
Harvey Cohen
*Grant, M. P. S.: Cytology in Prevention of Cancer of Cervix, p. 1637. MacGregor and Baird: Detection of Cervical Carcinoma in the General Population, p. 1631. A screening program for cervical carcinoma in Aberdeen during 1961 yielded 8,010 smears. Smears were obtained from parous women between the ages of 25 and 60 who were hospitalized on general hospital wards and from married women of the same age group who were under the care of three family physicians. Eighteen cases of clinically unsuspected preinvasive or early invasive carcinoma were detected. In data collected in Aberdeen, among women in the 25 to 60 age group, the mean age at the time of the diagnosis of a preinvasive cervical lesion was 39.6 years, of an invasive lesion, 43.6 years, and of a clinically detectable lesion, 48.3 years. On the basis of these figures, the authors suggest that rescreening of individuals be carried out at intervals of 5 years. The cost of diagnosing one case of cervical carcinoma under such a program is calculated to amount to 59 pounds. The cases of cervical carcinoma detected by the screening technique were by and large in women of high parity, who were in a low socioeconomic group. Since these women are the least likely to respond to invitations to appear for screening smears, the family physician's position is stressed in encouraging cytologic detection among his patients. Edward E. Wallach
Grant: Cytology in Prevention of Cancer of Cervix, p. 1637. The results of a study of cervical cytology in a group of 3,366 patients is presented. The group included 35 patients with clinically obvious cervical carcinoma and 275 patients clinically suspected of having cervical cancer. Five carcinomas were detected in the latter group. In the remaining patients there were 35 unsuspected cervical malignancies ( 1.04 per cent incidence). In all there were 75 malignant lesions. The average age of the 31 patients with in situ carcinoma was 40.0 years and of the 44 patients with invasive carcinoma, 55.5 years. High parity in this series did not appear to have an influence on the development of cervical carcinoma. Unsuspected cancers were found equally in patients with cervical erosions and in those without erosions. The 15.5 year difference in the mean age of the patients in the in situ cancer and invasive cancer groups
Selected abstracts 563
supports the view that m situ carcinoma progresses to invasiveness. Edward E. Wallach
Canadian Medical Association Journal Vol. 87, No. 12. *Ives, E.: Thalidomide and Anal Abnormalities, p. 670. lves: Thalidomide and Anal Abnormalities, p. 670. Two cases of severe anal stenosis in newborn infants are reported. Each mother had been given thalidomide between the third and eighth weeks of gestation. In one case the exact amount and time of administration was known. The embryology of the anus is reviewed, and it is postulated that the patients received the teratogenic agent after the formation of the limbs and during the canalization of the anal canal. A need for vigorous testing of drugs given to pregnant patients is urged.
Harvey Cohen No. 13. *Frazer, F. C.: Drug Induced Teratogenesis, p. 683. *Ringrose, C. A. D.: The Obstetrical Use of Ergot: A Violation of the Doctrine "Primum Non Nocere," p. 712. Frazer: Drug Induced Teratogenesis, p. 683. The author relates certain principles established in experimental teratology to the problem of teratogenesis in the human. Each teratogen is thought to produce its re· suits by specific pharmacological action on par· ticular embryonic tissues. The malformation pro· duced depends upon the agent, the dose, the spe· cies, the genetic constitution of both the mother and the embryo, and the stage of development. Attention is called to certain drugs given prenatally which have adverse postnatal effects such as some hypertensive agents that produce hypertension in the offspring of rats. A summation effect of two teratogens which individually do not produce malformations, but which together do, is discussed. A list of teratogenic drugs in animals is presented, as well as those suspected or known in humans. Trials of therapy, from implantation to term, of new drugs in experimental animals would be beneficial, in that possible dangers could be uncovered which may also be present in humans. The author stresses the need of a program
564
Selected abstracts
whereby all drugs given to pregnant women are recorded and the infants arc examined for possible harmful effects. No medication not definitely indicated should be administered tn pregnant women. Harvey Cohen
Ringrose: Obstetrical Use of Ergot: Violation of the Doctrine "Primum Non Nocere," p. i!2. The death of a 17-year-old primigravida, attributed to the use of intravenous ergonovinP maleate, 0.2 mg., is presented. The patient had a normal prenatal course; labor and delivery ·were spontaneously facilitated by a pudendal block of I per cent lidocaine, without any vascoconstrictor drug and episiotomy. The oxytocic agent was given with the crowning of the hPad following which the patient became nauseated, retched, and developed hypertmsion which pe-rsisted for 90 minutes. Because of a persistent heaclach(' a spinal tap was clone on the second postpartum clay which revealed bloody spinal fluid. Bilateral carotid angiograms were normal. The patient became semicomatose following the angiograms and shP died on the seventh postpartum clay. Postmortem examination revealed an intracerebral hemorrhage in the right frontal lobe rupturing into the subarachnoid space and right lateral ventricle. Any evidence of pre-existing lesions was obscured by hemorrhagP. The author attributes the death to th(· use of the ergot preparation. The role of ergot preparations in obstetrics is discussed. The use of oxytocic agents devoid of pressor pffects is advocated, as well as questioning the nf'ed of ergot derivatives and their prophylactic usc. Han'C}' Cohen No. 24 *Taylor, W. C.: Mortality and Morbidity of Exchange Transfusion, p. 1267.
Feb1 ua1 y 1:'1,
.-\m.
J.
1'!6-1
Ob>t. & Gvnec.
Taylor: Mortality and Morbidity of Exchange Transfusion, p. 1267. A study to ascertain both the morbidity and the mortality rates from exchange transfusions with citrated donor blood is presented. One hundred and four cases of infants requiring 150 exchange transfusions were reviewed. Seventy-two infants had Rh hemolytic disease, 22 had ABO hemolytic disease, and in I 0 the f'tiology was not ascrrtainecl. In 44 infants, representing ti2 exchange transfusions, electrocarcliograrns and biochemical determinations were performed. The-n· \Vf'rf' 8 total deaths. 3 of \\'hich \\·ere not considered to be n·latecl to the proceclurr. The rrmaining 5 deaths, representing a 4.8 per c••nt infant death rate are summarized. One death was directly related to the procedure of exchange transfusion, and in the othPr +, the proc('cltlff' was considered to be partly responsible for the death. Otht'r factors involved were anemia with a h\'moglobin of less than 10 Gm., prematurity, and hyperpotasscmia. In th(' ti2 transfusions, during which investigativt· procedures were performed, clinically recognizabiP disturbances wne present in 3 7 per cent. ThP majority of disturbances werr vomiting and n·tching·, 23 pPr cent; respiratory distress, 10 per cent; and convulsions or tf'tany, 8 per cent. The ratP of injPction influenced the incidence of retching and \·omiting, and thP author states that a (k~irable ratt· is 2 mi. per kilogram per rninutc. ThP hazard with tht· use of citratrcl donor blood is clisntssPcl and the use of donor blood rnorf' than 5 claYs old is conclemnccl because of , • ,..... "• uw mgn lt'\Wl orr porassmm. vonvulsions and• tetany art' prcwntecl if 1 mi. of I 0 per cent calcium gluconate is injected after each I 00 cr. of blood has been exchanged. .I
I
•
I
1
1
Harvey Cohen