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Transient symptomatic subendocardial ischemia during intravenous magnesium sulfate tocolytic therapy
Upper vaginectomy
Volume 166 Number 1, Part 1
20. 21. 22. 23. 24.
ment of vaginal intraepithelial neoplasia after hysterectomy. Br] Obstet GynaecoI1984;91:707-11. Curtin ]P, Twiggs LB, Julian TM. Treatment of vaginal intraepithelial neoplasia with the CO 2 laser. ] Reprod Med 1985;30:942-4. Lenehan PM, Meffe F, Lickrish GM. Vaginal intraepithelial neoplasia: biologic aspects and management. Obstet Gynecol 1986;68:333-7. Stuart GCE, Flagler EA, Nation]G, Dugan M, Robertson DI. Laser vaporization of vaginal intraepithelial neoplasia. AM] OBSTET GYNECOL 1988;158:240-3. Krebs HB. Treatment of vaginal intraepithelial neoplasia with laser and topical 5-ftuorouracil. Obstet Gynecol 1989;73:657-60. Audet-Lapointe P, Body G, Vauclair R, Drovin P, Ayoub ]. Vaginal intraepithelial neoplasia. Gynecol Oncol 1990;36:232-9.
25. Lee RA, Symmonds RE. Recurrent carcinoma in situ of the vagina in patients previously treated for in-situ carcinoma of the cervix. Obstet Gynecol 1976;48:61-4. 26. Woodruff ]D, Parmley TH, Julian CG. TopICal 5-ftuorouracil in the treatment of vaginal cartinoma in-situ. GynecoIOncoI1975;3:124-32. 27. Cavanagh D, Ruffolo EH, Marsden DE. Gynecologic cancer: a clinicopathologic approach. Norwalk, Connecticut: Appleton-Century-Crofts, 1985:47. 28. Peters WA, Kumar NB, Morley GW. Microinvasive carcinoma of the vagina: a distinct clinical entity? AM] OBSTET GYNECOL 1985;153:505-7. 29. Eddy GL, Singh KP, Gansler TS. Superficially invasive carcinoma of the vagina following treatment for cervical cancer: a report of six cases. Gynecol Oncol 1990;36: 376-9.
Transient symptomatic subendocardial ischemia during intravenous magnesium sulfate tocolytic therapy David M. Sherer, MD, Paul R. Cialone, MD, Jacques S. Abramowicz, MD, and James R. Woods, Jr., MD Rochester, New York Although ~-sympathomimetic tocolytic therapy has been associated with transient subendocardial ischemia, magnesium sulfate has rarely been noted to cause acute chest pain and is, in fact, known to improve myocardial perfusion in patients with variant angina. We believe this report represents the first case In which intravenous magnesium sulfate administered as a tocolytlc agent caused acute chest pain accompanied by transient electrocardiographic evidence of SUbendocardial ischemia. (AM J OSSTET GVNECOL 1992;166:33-5.)
Key words: Preterm labor, magnesium sulfate, myocardial ischemia Magnesium sulfate is a successful, inexpensive, and relatively nontoxic tocolytic agent with few side effects. The exact mechanism of its tocolytic activity is unclear. The incidence of acute chest pain in association with this therapy is low and has been reported at 1.1 %. We report the first documentation of acute chest pain accompanied by electrocardiographic signs of transient subendocardial ischemia occurring in conjunction with this regimen. From the DIVzsion of Maternal-Fetal Medzcine, Department of Obstetrics and Gynecology, Strong Memorial Hospital, The Umverslty of Rochester School of MediCIne and Dentistry. Received for publzcation May 28, 1991; accepted June 17, 1991. Reprint requests: David M. Sherer, MD, DIViSIOn of Maternal-Fetal Medzcme, Department of ObstetriCs and G_~necology, Strong MemOrial Hospital, The University of Rochester School and Medicine and Dentistry, 601 Elmwood Ave., Box 668, Rochester, NY 14642-8668. 6/1 /31815
Case report A 29-year-old Oriental woman, gravida 1, para 0, was admitted to labor and delivery at Strong Memorial Hospital because of preterm labor at 35 weeks 1 day of gestation. Her medical history was unremarkable, and her pregnancy was uneventful until she was seen on this occasion. Physical examination 4 hours before her referral disclosed the uterine cervix to be 90% effaced and dilated to 1 em. On admission, she was noted to be in good general health. Blood pressure was 110/65 mm Hg. The cervix was 90% effaced and dilated to 2 to 3 cm with the vertex presenting at S - 3 station. Although she initially responded to intravenous hydration, the uterine contractions recurred, and intravenous magnesium sulfate was administered at a rate of 3 gm/hr after a loading dose of 4 gm. Ten hours after this treatment was initiated, the patient began complaining of nonradiating substernal chest pain. No respiratory distress was noted, and blood pressure was
33
34
Sherer et al.
January 1992 Am J Obstet Gynecol
STRONG HE/lOIIJAI. HOSPlTAL
aVR
i:
vz
aill
I
'
I
I
,
I
'
:JVF
I'
i
I
I
V3
Fig. 1. Electrocardiogram during acute chest pain. Note inverted T waves in leads L, and V I through V, (speed 25 em / sec, voltage 1 em = 1 mY).
80/50 mm Hg with a heart rate of 100 beats/min. Electrocardiographic examination revealed a normal sinus rhythm at 84 beats/min with inverted T waves in L, and V, through V,leads (Fig. 1). Chest roentgenogram was normal. Laboratory evaluation revealed hemoglobin 12.2 gm, hematocrit 36%, sodium 135 mEq/L, potassium 3.9 mEq/L, glucose 93 mg /dl, creatine kinase 114 mD / ml (normal 0 to 122). MB (myocardial component) isozyme fraction 5% (normal). Serum magnesium level was 6.3 mEq/L. The intravenous magnesium sulfate was decreased to a rate of 2 gm/hr with resolution of chest pain, although a repeat electrocardiogram continued to demonstrate the inverted T waves. After 30 hours magnesium sulfate was gradually tapered successfully and discontinued with resolution of the electrocardiographic changes. The patient was discharged on day 3 after a normal echocardiogram. At 41 weeks 3 days' gestation, because of an arrest of the second stage of labor, a vacuum extraction was performed, with the delivery of a male infant weighing 3240 gm with Apgar scores of 8 and 9 at 1 and 5 minutes, respectively.
Comment [3-Sympathomimetic therapy for preterm labor has been associated with symptomatic and asymptomatic myocardial ischemia that appears to be localized in the subendocardial region. Subendocardial oxygen supply may be compromised during [3-sympathomimetic administration. This is thought to be a result of induced tachycardia resulting in a shortened diastole, i.e., the time of myocardial perfusion. and the placenta's effect on peripheral vascular resistance with diminished aortic diastolic blood pressure. In many centers magnesium
sulfate has replaced [3-sympathomimetic therapy as the first-line drug for tocolysis of preterm labor. To date, there have been no reported cases of myocardial ischemia during magnesium sulfate administration, when it was used for this purpose. Intravenous magnesium sulfate is known to have antiarrhythmic effects and has, in fact, been used as a possible protective agent in patients with acute myocardial infarction, reducing conduction disturbances and in-hospital mortality in these patients. Furthermore, intravenous magnesium sulfate suppresses exercise-induced angina.' The size of the myocardial perfusion defect as measured by thallium 201 scintigraphy was significantly less in 13 patients with variant angina receiving magnesium sulfate than in II control patients receiving placebo.' The beneficial effect of magnesium in patients with variant angina is thought most likely to represent improvement of regional myocardial blood flow by suppression of coronary artery spasm. It is therefore of significance that acute chest pain with transient myocardial ischemia and associated electrocardiographic changes occurred during administration of this drug for tocolysis of preterm labor. This event may have resulted from hypotension as a secondary effect of intravenous magnesium sulfate, compounded by a physiologic reduction in diastolic blood pressure normally occurring in pregnancy, which led to a transient but substantial decrease in subendocardial perfusion. Dandavino et aU have previously shown that bolus administration of magnesium sulfate to control levels occurred within 5 minutes of bolus injection and no change in blood pressure occurred
Volume 166 Number 1, Part I
during subsequent infusion of magnesium sulfate at 2 or 4 gm/hr. In our case symptoms and associated electrocardiographic changes were noted 10 hours into treatment. The mechanism of this drug-related sequela remains to be deciphered. Nevertheless, because of the widespread use of magnesium sulfate in pregnancy, this case is reported to bring attention to this seemingly rare drug event.
Subendocardial ischemia during magnesium tocolysis
REFERENCES I. Kuglyama K, Yasue H, Okumura K, et al. SuppressIOn of
exercise-induced angina by magnesium sulfate in patients with variant angina.] Am Coll CardioI1988;12:1177-83. 2. Dandavino A, Woods ]R, Murayama K, Brinkman CR, Assali NS. Circulatory effects of magnesium sulfate in normotensive and renal hypertensive pregnant sheep. AM] OBSTET GYNECOL 1977;127:769-74.
Possible transplacental transmission of human papillomaviruses Chih-Jen Tseng, MD,. Chieh-Yu Lin, BS," Ruey-Ling Wang, BS,b Li-Ju Chen, BS,a Ya-Li Chang, MS,b T'sang-T'ang Hsieh, MD,a and Chia C. Pao, PhD b Taipei, Tazwan, Repubhc of China OBJECTIVE: The objective of this study was to examine the possibility of Intrautenne human papillomavirus infection of fetuses by transplacental transmission of human papiliomavirus before delivery. STUDY DESIGN: Specimens of cervicovaginal cells and peripheral blood mononuclear cells were obtained from 52 consecutive pregnant women in the third trimester of pregnancy. Cord blood specimens were also obtained from the neonates born to these mothers. Presence of human papillomavtrus types 16 and 18 deoxyribonucleic acid was analyzed by an in vitro enzymatic deoxynbonuclelc acid amplification method. RESULTS: Human papillomavirus type 16 deoxyribonucleic aCid was found In 6 (11.5%) cervlcovaginal and in 9 (17.3%) peripheral blood mononuclear cell specimens. Seven cord blood specimens from neonates born to mothers who were positive for penpheral blood mononuclear cell human papillomavtrus type 16 deoxyribonucleic acid were found to contain human papillomavirus type 16 deoxyribonucleic acid. One cervlcovaginal and two peripheral blood mononuclear cell specimens contained human papillomavirus type 18 deoxyribonucleic acid, but none of the cord blood specimens contained human papillomavirus type 18 deoxyribonucleic acid. CONCLUSION: These results seem to suggest possible transplacental transmission of the virus and the potential aSSOCiation of such transmiSSion with the status of human papillomavirus in peripheral blood mononuclear cells. (AM J OBSTET GVNECOL 1992;166:35-40.)
Key words: Human papillomavirus, transplacental transmission, polymerase chain reaction (peR), peripheral blood mononuclear cells Depending on the detection method used and the type of tissue examined, between 10% and 60% of clinically and histologically normal cervical specimens from a general population were found to contain human papillomavirus (HPV) deoxyribonucleic acid (DNA).1.5 From the Department of Obstetncs and G.vnecologya and BIOchemIStry, b Chang Gung Memonal Hospital and Medical College. Supported by medical research grants CMRP-235 and CMRP-286 from Chang Gung Medical College and Memorial Hospital, Tazpei, Tazwan, Republzc of Chma (awarded to e.C.P.). Received for publicatIOn January 22, 1991; revISed Apn115, 1991; accepted May 28, 1991. Professor Chza C. Pao, Department of BIOchemistry, Chang Gung Medical College, 259 Wen Hwa Road. KwelShan, TaoYuan. Taiwan. Republic of Chzna. 6/1131259
Although most of these infections are asymptomatic and subclinical in nature and the clinical and biologic significance of these findings is not clear, the prevalence of HPV even among the general population is probably quite high. Management of pregnant patients with HPV infections takes on additional importance because of the possibility of maternal-fetal transmission. The issue of possible maternal-fetal HPV transmission is a pressing concern for pregnant patients because several reports have suggested that the incidence of genital HPV infection is higher in pregnant women than in nonpregnant women. 6 . g Given that the behavior of urogenital human papillomavirus infections during pregnancy is not clear and that the exact mode and risk of the maternal-fetal HPV transmission in clinically 35
Volume 166 Number 1, Part 1
20. 21. 22. 23. 24.
ment of vaginal intraepithelial neoplasia after hysterectomy. Br] Obstet GynaecoI1984;91:707-11. Curtin ]P, Twiggs LB, Julian TM. Treatment of vaginal intraepithelial neoplasia with the CO 2 laser. ] Reprod Med 1985;30:942-4. Lenehan PM, Meffe F, Lickrish GM. Vaginal intraepithelial neoplasia: biologic aspects and management. Obstet Gynecol 1986;68:333-7. Stuart GCE, Flagler EA, Nation]G, Dugan M, Robertson DI. Laser vaporization of vaginal intraepithelial neoplasia. AM] OBSTET GYNECOL 1988;158:240-3. Krebs HB. Treatment of vaginal intraepithelial neoplasia with laser and topical 5-ftuorouracil. Obstet Gynecol 1989;73:657-60. Audet-Lapointe P, Body G, Vauclair R, Drovin P, Ayoub ]. Vaginal intraepithelial neoplasia. Gynecol Oncol 1990;36:232-9.
25. Lee RA, Symmonds RE. Recurrent carcinoma in situ of the vagina in patients previously treated for in-situ carcinoma of the cervix. Obstet Gynecol 1976;48:61-4. 26. Woodruff ]D, Parmley TH, Julian CG. TopICal 5-ftuorouracil in the treatment of vaginal cartinoma in-situ. GynecoIOncoI1975;3:124-32. 27. Cavanagh D, Ruffolo EH, Marsden DE. Gynecologic cancer: a clinicopathologic approach. Norwalk, Connecticut: Appleton-Century-Crofts, 1985:47. 28. Peters WA, Kumar NB, Morley GW. Microinvasive carcinoma of the vagina: a distinct clinical entity? AM] OBSTET GYNECOL 1985;153:505-7. 29. Eddy GL, Singh KP, Gansler TS. Superficially invasive carcinoma of the vagina following treatment for cervical cancer: a report of six cases. Gynecol Oncol 1990;36: 376-9.
Transient symptomatic subendocardial ischemia during intravenous magnesium sulfate tocolytic therapy David M. Sherer, MD, Paul R. Cialone, MD, Jacques S. Abramowicz, MD, and James R. Woods, Jr., MD Rochester, New York Although ~-sympathomimetic tocolytic therapy has been associated with transient subendocardial ischemia, magnesium sulfate has rarely been noted to cause acute chest pain and is, in fact, known to improve myocardial perfusion in patients with variant angina. We believe this report represents the first case In which intravenous magnesium sulfate administered as a tocolytlc agent caused acute chest pain accompanied by transient electrocardiographic evidence of SUbendocardial ischemia. (AM J OSSTET GVNECOL 1992;166:33-5.)
Key words: Preterm labor, magnesium sulfate, myocardial ischemia Magnesium sulfate is a successful, inexpensive, and relatively nontoxic tocolytic agent with few side effects. The exact mechanism of its tocolytic activity is unclear. The incidence of acute chest pain in association with this therapy is low and has been reported at 1.1 %. We report the first documentation of acute chest pain accompanied by electrocardiographic signs of transient subendocardial ischemia occurring in conjunction with this regimen. From the DIVzsion of Maternal-Fetal Medzcine, Department of Obstetrics and Gynecology, Strong Memorial Hospital, The Umverslty of Rochester School of MediCIne and Dentistry. Received for publzcation May 28, 1991; accepted June 17, 1991. Reprint requests: David M. Sherer, MD, DIViSIOn of Maternal-Fetal Medzcme, Department of ObstetriCs and G_~necology, Strong MemOrial Hospital, The University of Rochester School and Medicine and Dentistry, 601 Elmwood Ave., Box 668, Rochester, NY 14642-8668. 6/1 /31815
Case report A 29-year-old Oriental woman, gravida 1, para 0, was admitted to labor and delivery at Strong Memorial Hospital because of preterm labor at 35 weeks 1 day of gestation. Her medical history was unremarkable, and her pregnancy was uneventful until she was seen on this occasion. Physical examination 4 hours before her referral disclosed the uterine cervix to be 90% effaced and dilated to 1 em. On admission, she was noted to be in good general health. Blood pressure was 110/65 mm Hg. The cervix was 90% effaced and dilated to 2 to 3 cm with the vertex presenting at S - 3 station. Although she initially responded to intravenous hydration, the uterine contractions recurred, and intravenous magnesium sulfate was administered at a rate of 3 gm/hr after a loading dose of 4 gm. Ten hours after this treatment was initiated, the patient began complaining of nonradiating substernal chest pain. No respiratory distress was noted, and blood pressure was
33
34
Sherer et al.
January 1992 Am J Obstet Gynecol
STRONG HE/lOIIJAI. HOSPlTAL
aVR
i:
vz
aill
I
'
I
I
,
I
'
:JVF
I'
i
I
I
V3
Fig. 1. Electrocardiogram during acute chest pain. Note inverted T waves in leads L, and V I through V, (speed 25 em / sec, voltage 1 em = 1 mY).
80/50 mm Hg with a heart rate of 100 beats/min. Electrocardiographic examination revealed a normal sinus rhythm at 84 beats/min with inverted T waves in L, and V, through V,leads (Fig. 1). Chest roentgenogram was normal. Laboratory evaluation revealed hemoglobin 12.2 gm, hematocrit 36%, sodium 135 mEq/L, potassium 3.9 mEq/L, glucose 93 mg /dl, creatine kinase 114 mD / ml (normal 0 to 122). MB (myocardial component) isozyme fraction 5% (normal). Serum magnesium level was 6.3 mEq/L. The intravenous magnesium sulfate was decreased to a rate of 2 gm/hr with resolution of chest pain, although a repeat electrocardiogram continued to demonstrate the inverted T waves. After 30 hours magnesium sulfate was gradually tapered successfully and discontinued with resolution of the electrocardiographic changes. The patient was discharged on day 3 after a normal echocardiogram. At 41 weeks 3 days' gestation, because of an arrest of the second stage of labor, a vacuum extraction was performed, with the delivery of a male infant weighing 3240 gm with Apgar scores of 8 and 9 at 1 and 5 minutes, respectively.
Comment [3-Sympathomimetic therapy for preterm labor has been associated with symptomatic and asymptomatic myocardial ischemia that appears to be localized in the subendocardial region. Subendocardial oxygen supply may be compromised during [3-sympathomimetic administration. This is thought to be a result of induced tachycardia resulting in a shortened diastole, i.e., the time of myocardial perfusion. and the placenta's effect on peripheral vascular resistance with diminished aortic diastolic blood pressure. In many centers magnesium
sulfate has replaced [3-sympathomimetic therapy as the first-line drug for tocolysis of preterm labor. To date, there have been no reported cases of myocardial ischemia during magnesium sulfate administration, when it was used for this purpose. Intravenous magnesium sulfate is known to have antiarrhythmic effects and has, in fact, been used as a possible protective agent in patients with acute myocardial infarction, reducing conduction disturbances and in-hospital mortality in these patients. Furthermore, intravenous magnesium sulfate suppresses exercise-induced angina.' The size of the myocardial perfusion defect as measured by thallium 201 scintigraphy was significantly less in 13 patients with variant angina receiving magnesium sulfate than in II control patients receiving placebo.' The beneficial effect of magnesium in patients with variant angina is thought most likely to represent improvement of regional myocardial blood flow by suppression of coronary artery spasm. It is therefore of significance that acute chest pain with transient myocardial ischemia and associated electrocardiographic changes occurred during administration of this drug for tocolysis of preterm labor. This event may have resulted from hypotension as a secondary effect of intravenous magnesium sulfate, compounded by a physiologic reduction in diastolic blood pressure normally occurring in pregnancy, which led to a transient but substantial decrease in subendocardial perfusion. Dandavino et aU have previously shown that bolus administration of magnesium sulfate to control levels occurred within 5 minutes of bolus injection and no change in blood pressure occurred
Volume 166 Number 1, Part I
during subsequent infusion of magnesium sulfate at 2 or 4 gm/hr. In our case symptoms and associated electrocardiographic changes were noted 10 hours into treatment. The mechanism of this drug-related sequela remains to be deciphered. Nevertheless, because of the widespread use of magnesium sulfate in pregnancy, this case is reported to bring attention to this seemingly rare drug event.
Subendocardial ischemia during magnesium tocolysis
REFERENCES I. Kuglyama K, Yasue H, Okumura K, et al. SuppressIOn of
exercise-induced angina by magnesium sulfate in patients with variant angina.] Am Coll CardioI1988;12:1177-83. 2. Dandavino A, Woods ]R, Murayama K, Brinkman CR, Assali NS. Circulatory effects of magnesium sulfate in normotensive and renal hypertensive pregnant sheep. AM] OBSTET GYNECOL 1977;127:769-74.
Possible transplacental transmission of human papillomaviruses Chih-Jen Tseng, MD,. Chieh-Yu Lin, BS," Ruey-Ling Wang, BS,b Li-Ju Chen, BS,a Ya-Li Chang, MS,b T'sang-T'ang Hsieh, MD,a and Chia C. Pao, PhD b Taipei, Tazwan, Repubhc of China OBJECTIVE: The objective of this study was to examine the possibility of Intrautenne human papillomavirus infection of fetuses by transplacental transmission of human papiliomavirus before delivery. STUDY DESIGN: Specimens of cervicovaginal cells and peripheral blood mononuclear cells were obtained from 52 consecutive pregnant women in the third trimester of pregnancy. Cord blood specimens were also obtained from the neonates born to these mothers. Presence of human papillomavtrus types 16 and 18 deoxyribonucleic acid was analyzed by an in vitro enzymatic deoxynbonuclelc acid amplification method. RESULTS: Human papillomavirus type 16 deoxyribonucleic aCid was found In 6 (11.5%) cervlcovaginal and in 9 (17.3%) peripheral blood mononuclear cell specimens. Seven cord blood specimens from neonates born to mothers who were positive for penpheral blood mononuclear cell human papillomavtrus type 16 deoxyribonucleic acid were found to contain human papillomavirus type 16 deoxyribonucleic acid. One cervlcovaginal and two peripheral blood mononuclear cell specimens contained human papillomavirus type 18 deoxyribonucleic acid, but none of the cord blood specimens contained human papillomavirus type 18 deoxyribonucleic acid. CONCLUSION: These results seem to suggest possible transplacental transmission of the virus and the potential aSSOCiation of such transmiSSion with the status of human papillomavirus in peripheral blood mononuclear cells. (AM J OBSTET GVNECOL 1992;166:35-40.)
Key words: Human papillomavirus, transplacental transmission, polymerase chain reaction (peR), peripheral blood mononuclear cells Depending on the detection method used and the type of tissue examined, between 10% and 60% of clinically and histologically normal cervical specimens from a general population were found to contain human papillomavirus (HPV) deoxyribonucleic acid (DNA).1.5 From the Department of Obstetncs and G.vnecologya and BIOchemIStry, b Chang Gung Memonal Hospital and Medical College. Supported by medical research grants CMRP-235 and CMRP-286 from Chang Gung Medical College and Memorial Hospital, Tazpei, Tazwan, Republzc of Chma (awarded to e.C.P.). Received for publicatIOn January 22, 1991; revISed Apn115, 1991; accepted May 28, 1991. Professor Chza C. Pao, Department of BIOchemistry, Chang Gung Medical College, 259 Wen Hwa Road. KwelShan, TaoYuan. Taiwan. Republic of Chzna. 6/1131259
Although most of these infections are asymptomatic and subclinical in nature and the clinical and biologic significance of these findings is not clear, the prevalence of HPV even among the general population is probably quite high. Management of pregnant patients with HPV infections takes on additional importance because of the possibility of maternal-fetal transmission. The issue of possible maternal-fetal HPV transmission is a pressing concern for pregnant patients because several reports have suggested that the incidence of genital HPV infection is higher in pregnant women than in nonpregnant women. 6 . g Given that the behavior of urogenital human papillomavirus infections during pregnancy is not clear and that the exact mode and risk of the maternal-fetal HPV transmission in clinically 35