Essential hypertension and pregnancy

ROBERT A. BEAR, MD, FRCP[C], FACP; NORMAN ERENRICH, MD

Approximately 10/0 of pregnancies are Ces medicaments doivent .tre choisis Hypertension complicated during pregnancy: by essential hypertension. avec soin afin d'eviter toute toxicit6 differential diagnosis During pregnancy the blood pressure foetale ou maternelle, et les diur6tiques often stabilizes or improves. In ainsi que les r6gimes hyposodes patients with sustained hypertension, devraient .tre evites durant Ia It is difficult to make a diagnosis prospective controlled studies have grossesse. Chez 20/a a 110/a des patientes of essential hypertension in a woman demonstrated enhanced fetal survival souffrant d'hypartension essentielle whose elevated blood pressure is when the blood pressure was controlled le probleme s'accentue tard durant Ia being evaluated for the first time with antihypertensive medication. Such grossesse; cette accel6ration peut .tre during pregnancy. The diagnosis can medication must be chosen carefully predite par Ia d6termination, chez Ia be made most confidently to avoid fetal and maternal when the toxicity, mere, des pressions art6rielles et des hypertension has been noted prior and diuretics and salt restriction during volumes intravasculaires moyens, t6t pregnancy should be avoided. Among to pregnancy and its genesis has been durant Ia grossesse. Le traitement determined. patients with essential hypertension de l'hypertension acc6l.r6e est identique In persons first noted to the problem accelerates late in a celui d'une pr6-eclampsie s6v.re. be hypertensive during pregnancy, m- pregnancy in 20/o to l10/o; the La perte foetale est considerable mais vestigation must be undertaken to acceleration may be predicted by elle peut .tre diminu6e par une separate those with underlying es- determination of maternal mean arterial surveillance foetale et maternelle suivie sential hypertension from those with pressures and intravascular volumes et un accouchement precoce contr6le. pre-existent chronic renal disease, early in pregnancy. The treatment of Pour Ia plupart des patientes souffrant pre-eclampsia or secondary hyper- accelerated hypertension is identical d'hypertension essentielle les risques to that of severe pre-eclampsia. Fetal tension. Edema and proteinuria are de Ia grossesse sont faibles, et more common pregnant loss is considerable but can be lessened l'hypertension essentielle n'est pas in women by careful fetal and maternal uniformement une contreindication a with any of these disorders, and since monitoring and early controlled delivery. Ia grossesse. investigative procedures must be lim- The risks of pregnancy in most patients ited during pregnancy accurate diag- with essential hypertension are small, Hypertension, the commonest med- nosis often must await radiologic and and essential hypartension is not a ical complication of pregnancy, may biopsy procedures uniform performed post contraindication to pregnancy. occur in association with a number partum. In such cases it is helpful of underlying disorders. In most to obtain prior medical histories and Environ lOb des grossesses sont series 70% of hypertensive preg- compliquees d'hypertenslon essentielle. summaries of previous medical as- Durant Ia grossesse Ia tension art6rielle nant women have pre-eclampsia or sessments. This information, along souvent se stabilise ou s'am6liore. eclampsia, 25% have essential hy- with the current clinical history and Chez des patientes souffrant d'hyper. pertension and 5% have underlying the results of physical examination, tension persistante, des 6tudes chronic renal disease.1" Looked at microscopic examination and culture prospectives contr8l6es ont d.montre another way, 3% to 4% of all preg- of the urine, and determination of une survie foetale am6llor.e lorsque nancies are complicated by hyper- serum concentrations of creatinine, Ia tension art6rielle a 6te contr8l6e tension due to pre-eclampsia or par une m6dication antihypertensive. electrolytes and uric acid (the last eclampsia, while 1% are complicated being normal or increased in eclamp- From the division of nephrology, by essential hypertension.' Essential tic syndromes) and 24-hour urine department of medicine, St. Michael's hypertension therefore is a not un- excretion of protein, often leads to Hospital and the University of Toronto common cause of elevated blood an accurate clinical diagnosis. In Reprint requests to: Dr. Robert A. Bear, pressure in pregnancy. In this article addition, 24-hour urine excretion of Division of nephrology, Department of the diagnosis, clinical course and vanillylmandelic acid, metanephrine medicine, St. Michael's Hospital, 30 medical management of this disorder normetanephrine Bond St., Toronto, Ont. M5B and should be 1W8 are reviewed. measured in women with previously 936 CMA JOURNAL/APRIL 22, 1978/VOL. 118 unevaluated severe hypertension, as hypertension develops late in preg- a number of new and interesting pheochromocytoma during pregnan- nancy, some women whose blood studies other investigators have dem- cy, though rare, is associated with pressure has been maintained at nor- onstrated that severe hypertension in extremely high maternal and fetal mal levels throughout early pregnan- pregnancy (essential hypertension, mortality.3 cy experience this complication.11'1' essential hypertension with acceler- Pregnant women with pre-existent Patients with essential hyperten- ated hypertension, or an eclamptic renal disease (except for patients with sion in whom accelerated hyperten- syndrome) is often accompanied by lupus nephritis4) are best managed sion develops late in pregnancy are clinical or laboratory evidence, or on the basis of the serum creatinine universally described as having su- both, of decreased intravascular vol- value before pregnancy or at the perimposed pre-eclampsia; however. ume.' Furthermore, there is evidence time of the first consultation during precise data (for example, from renal that in women with hypertension of pregnancy.' Women with even mild biopsy) to support this diagnosis are any type in whom the blood volume pre-eclampsia should be admitted to scanty.13 Examination of the placenta falls to expand normally early in hospital for careful monitoring, while in such cases reveals decreased pla- pregnancy the fetal outcome is poor." those with severe pre-eclampsia (hy- cental size and ischemic vascular Bletka and collaborators" have pertension, edema, proteinuria, oligu- changes compatible with either hy- demonstrated that normotensive na, hyperreflexia and abdominal pertension or pre-eclampsia.'4 How- women in whom pre-eclampsia pain) require hospitalization, seda- ever, the changes in clotting factors eventually develops have substantial tion, bed rest in the lateral decubitus that occur in women with pre- decreases in circulating plasma vol- position, adequate sodium adminis- eclampsia have not been demon- ume early in pregnancy. These tration, blood pressure monitoring strated in pregnant women with es- studies suggest that decreased intra- and control, constant and multifacet- sential hypertension." Until more vascular volume may lead to hor- ted fetal monitoring and early de- definitive information accumulates, monal and hemodynamic changes de- livery.6 Secondary hypertension dur- therefore, these patients are best de- signed to increase blood pressure and ing pregnancy is relatively rare and, scribed as having accelerated hyper- thereby preserve uteroplacental per- with the exception of pheochromo- tension, the pathophysiologic features fusion. Decreased intravascular vol- cytoma and sometimes coarctation of of which remain undetermined. ume therefore may be paradoxically the aorta, is best dealt with defini- In general, maternal mortality in associated with striking increases in tively post partum.7 Because it is the essential hypertension is low; how- blood pressure. In the future it may purpose of this review to discuss es- ever, maternal risk is increased by be possible to predict the patients sential hypertension in pregnancy, advanced maternal age, by long- with essential hypertension in whom the management of pregnancy in standing hypertension with hyperten- accelerated hypertension is likely to women with pre-existent renal dis- sion-mediated end-organ damage and develop by monitoring factors such ease, an eclamptic syndrome or sec- by the development of accelerated as the mean arterial pressure during ondary 'hypertension will not be de- hypertension. Infant birth weights the 2nd trimester and the degree to tailed further. and the incidence of fetal loss do which the intravascular volume ex- not differ substantially from normal pands in the early stages of preg- when the blood pressure of women nancy. Essential hypertension with mild essential hypertension de- creases or remains normal through- Management during pregnancy Pathophysiologic considerations out pregnancy.'6 However, in women It is clear that in pregnant women and course during pregnancy with persistent hypertension during with underlying essential hyperten- pregnancy, control of the hyperten- sion the outcome of pregnancy will In women with essential hyperten- sion with antihypertensive agents is be determined to a certain extent by sion the blood pressure may remaln of unequivocal value in terms of fetal the degree to which the blood pres- stable in early pregnancy or may survival.""7 When accelerated hyper- sure is adequately controlled. Avail- even fall (generating a false sense of tension develops the incidence of ability of new pharmacologic prep- security in the clinician); however, prematurity and of small infant size arations, advances in biochemical in most such women it will increase for gestational age is high and the and noninvasive methods of fetal sometime during the 2nd or 3rd tri- fetal mortality is strikingly m- monitoring, and increased under- mester, and in some instances severe creased.""8"6 The development of standing of the physiologic aspects of accelerated hypertension will de- abruptio placentae may also be more pregnancy have led to significant ad- velop. The frequency with which common in women with accelerated vances in management. severe accelerated hypertension oc- hypertension. It has become apparent, for ex- curs is controversial; early papers Since the cause of accelerated hy- ample, that salt restriction has no reported a rate as high as 30% ,. pertension in women with underlying place in the management of a preg- but more recent studies have sug- essential hypertension is not well un- nant woman with essential hyperten- gested a rate of 2% to 11 % 9,1o Al- derstood, it is impossible to state with sion, particularly since some inves- though better pharmacologic manage- accuracy in which persons it is likely tigators have demonstrated that these ment of hypertension throughout to develop. Page and Christianson'8"9 women have a decreased ability to gestation has undoubtedly been one believe that the mean arterial blood conserve sodium normally.23 Sodium important factor in the reduction of pressure in the 2nd trimester is of restriction may induce a fall in the the frequency with which accelerated predictive value in this regard. In intravascular volume resulting in a CMA JOURNAL/APRIL 22, 1978/VOL. 118 937 decrease in renal and uteroplacental and the dosage increased as required assessing whether the fetus is ma- perfusion. Through mechanisms de- to a maximum of 500 mg four times ture.TM Other tests that are important tailed above, this may result in a daily. Hydralazine, a vasodilating as indexes of the viability of the paradoxic increase in blood pressure agent, may be used in a daily dose uteroplacental unit include examina- despite a decrease in intravascular of up to 300 mg. This medication tion of the amniotic fluid for meco- volume."0'2 It has been suggested, increases cardiac output and renal nium staining (this may suggest fetal in fact, that liberal ingestion of salt and uterine blood flow,'0 and is a anoxia), serial determination of uri- may be beneficial in the maintenance good antihypertensive agent for use nary estriol excretion'5 and of human of good blood pressure control dur- during pregnancy. In nonpregnant placental lactogen values,'0 and per- ing pregnancy.. persons hydralazine is most effec- formance of oxytocin challenge tests'. Although no definitive data exist tively combined with the p-blocking and "nonstress tests".'8 (Concomitant that define the optimum blood pres- agent propranolol. However the lat- administration of antibiotics may ar- sure to be maintained throughout ter has recently been linked with tefactually decrease urinary estriol pregnancy in a woman with essential cases of multiple fetal abnormali- excretion in pregnant women.'9) hypertension, in recent years the in- ties,30'31 and it may cause neonatal Baseline antihypertensive therapy dications for initiation of antihyper- respiratory depression.'2 The com- should be continued in these patients, tensive therapy have been better de- bination of hydralazine and propran- and additional medication should be fined. Because too vigorous pharma- olol, therefore, generally should be used to maintain the diastolic blood cologic lowering of the systemic avoided during pregnancy. pressure below 110 mm Hg. When blood pressure may impair utero- The use of reserpine and guane- additional medication is required we placental perfusion, initiation of anti- thidine in pregnancy is limited by prefer to use diazepam along with hypertensive therapy in pregnant the side effects of these agents. There hydralazine administered parenter- women is commonly deferred until are many well recognized side effects ally.40 Magnesium sulfate has a long the diastolic pressure exceeds 100 of reserpine therapy that occur in history of success in patients with mm Hg in the 2nd trimester or 110 both pregnant and nonpregnant pa- accelerated hypertension.6 It has anti- mm Hg in the 3rd trimester, and it tients; in addition, during pregnancy convulsant, hypotensive and sedative should be the clinician's aim to main- maternal sensitivity to seizures is in- properties. A therapeutic blood con- tain the diastolic blood pressure at creased, and neonatal anorexia, nasal centration of 6 to 8 mEq/L should no less than 90 mm Hg. stuffiness and secondary cyanosis and be achieved and there should be fre- No antihypertensive medication is respiratory distress may occur (neo- quent clinical monitoring for magne- uniquely qualified for use in preg- nates are obligate nose-breathers). sium intoxication. Pennington and nancy. During pregnancy, diuretic- The marked orthostatic hypotension Picker41 and others have reported induced volume depletion may inter- that frequently accompanies guane- success with intravenous administra- fere with renal and uteroplacental thidine administration decreases this tion of diazoxide, a nondiuretic ben- perfusion and, in accordance with drug's usefulness in pregnancy. Gb- zothiadiazine. This medication is the mechanisms outlined above, this nidine and bethanidine have not had given rapidly as an intravenous bolus may result in a syndrome simulating wide use in pregnancy, so their in a dose of 5 mg/kg, and it may be worsening pre-eclampsia.'0 Thiazide safety is largely unknown. given again in 30 minutes and then diuretics have also been implicated every few hours as required. Al- in fatal maternal hemorrhagic Development of accelerated pan- hypertension though effective in controlling ac- creatitis'0 and hyponatremia. and in celerated hypertension, this medica- neonatal thrombocytopenia.'7 More In pregnant women with under- tion causes decreased uterine activity, potent diuretics acting on the loop of lying essential hypertension acceler- so that simultaneous administration Henle have an even stronger tendency ated hypertension occasionally devel- of oxytocin may be necessary. In ad- to produce depletion of the extracel- ops during pregnancy, most common- dition, diazoxide may result in so- lular fluid volume and electrolyte im- ly in the 2nd or 3rd trimester. The dium retention and occasionally fetal balance. Furthermore, furosemide has management of such patients is simi- and maternal hyperglycemia. Al- been reported to cause congenital ab- lar to the management of patients though therapy with cbonidine41 and normalities in experiments with ani- with severe pre-eclampsia. They bethanidine4' given intravenously has mals.'0 During pregnancy, therefore, should be hospitalized and rest in been reported to be successful in diuretic agents generally should be bed in the lateral decubitus position. avoided, the management of pregnant women although administration of Sedatives may be administered. As with accelerated hypertension, ex- powerful loop diuretics may be life- it is becoming clear that depletion of perience with these agents is limited; saving in the treatment, for example, the intravascular fluid volume often of acute left ventricular failure other regimens are probably safer asso- contributes to the hypertension in and more effective. Sodium nitro- ciated with accelerated hypertension. these patients, such depletion should prusside Alpha-methyldopa is is an important drug in the an effective be sought, and if found it should be management of hypertensive crises and safe antihypertensive agent in corrected with salt administration.'0"' nonpregnant pregnancy.11'11 With this medication in persons; however, the Fetal monitoring by standard means possible harmful effects on the fetus regional blood flow to the kidneys is essential. Ultrasonography and and uterus is relatively well of the small amount of cyanide re- pre- amniocentesis with determination of leased by the metabolism of this drug served.'.' An initial dose of 125 mg lecithin-sphingomyelin ratios in the three times daily can be prescribed prohibits its use during pregnancy. amniotic fluid will prove helpful in Ganglionic blockers such as pento- 938 CMA JOURNAL/APRIL 22, 1978/VOL. 118 linium tartrate should be avoided, as cardiovascular or renal disease, or 18. PAGE EW, CHRISTIANSON R: The im- they cause meconium ileus in the had poorly controlled hypertension pact of mean arterial pressure in the middle trimester upon the outcome newborn. prior to pregnancy, in most women of pregnancy. Am J Obstet Gynecol If the results of ultrasonography essential hypertension should no 125: 740, 1976 and biochemical study of amniotic longer be considered a contraindica- 19. Idem: Influence of blood pressure fluid suggest that the fetus is mature, tion to pregnancy. changes with and without proteinuria upon outcome of pregnancy. Am J delivery should be undertaken as Obstet Gynecol 126: 821, 1976 soon as the mother's blood pressure References 20. SOFFRONOFF EC, KAUFMANN BM, has been stabilized. Alternatively, CONNAUGHTON JF: Intravascular vol- should the amniotic fluid assessment, 1. BROWNE RJ: Chronic hypertension ume determinations and fetal outcome and pregnancy (William Meredith in hypertensive diseases of pregnancy. urinary estriol values or other para- Fletcher Shaw memorial lecture). Br Am J Obstet Gynecol 127: 4, 1977 meters of fetal welfare indicate fetal Med J 2: 283, 1947 21. ARIAS F: Expansion of intravascular distress, or should the blood pres- 2. WELLEN I: The infant mortality in volume and fetal outcome in patients sure be difficult to control, delivery specific hypertensive disease of preg- with chronic hypertension in pregnan- should be undertaken irrespective of nancy in essential hypertension. Am cy. Am J Obstet Gynecol 123: 610, J Obstet Gynecol 66: 36, 1953 1975 fetal maturity. If delivery is indicated 3. Fox LP, GRANDI J, JOHNSON AH, et 22. BLETKA M, HLAVATY V, BENDL J, et and vaginal delivery is not feasible, al: Pheochromocytoma associated al: Volume of whole blood and ab- cesarean section should be per- with pregnancy. Am J Obstet Gynecol solute amount of serum proteins in formed. 104: 288, 1969 the early stage of late toxemia of 4. BEAR RA: Pregnancy and lupus pregnancy. Am J Obstet Gynecol 106: nephritis: a detailed report of six 10, 1970 Conclusions cases with a review of the literature. 23. SARLES HE, HILL SS, LEBLANC AL, et Obstet Gynecol 47: 715, 1976 al: Sodium excretion patterns during 5. Idem: Pregnancy in patients with and following intravenous sodium In managing pregnant women with renal disease: a study of 44 cases. chloride loads in normal and hyper- mild to moderate essential hyperten- Obstet Gynecol 48: 13, 1976 tensive pregnancies. Am J Obstet sion the clinician should try to 6. SPEROFF L: Toxemia of pregnancy: Gynecol 102: 1, 1968 achieve a stable diastolic blood pres- mechanism and therapeutic manage- 24. FOOTE RG, LUDBROOK APR: The use ment. Am I Cardiol 32: 582, 1973 of a liberal salt diet in pre-eclamptic sure of 90 to 100 mm Hg. Sodium 7. FERRIS T: Toxemia and hypertension, toxemia and essential hypertension restriction and diuretic agents gen- in Medical Complications During with pregnancy. NZ Med J 77: 242, erally should be avoided. Antihyper- Pregnancy, 1st ed, BURROW GN, FER- 1973 tensive therapy is best initiated with RIS TF (eds), Philadelphia, Saunders, 25. PALOMAK1 JE, LINDHEIMER MD: So- a-methyldopa in a dose of up to 1975, pp 53-104 dium depletion simulating deteriora- 8. CHESLEY LC, ANMTro JE: Pregnancy tion in a toxemic pregnancy. N Engi J 2 g/d, and hydralazine without pro- in the patient with hypertensive dis- Med 282: 88, 1970 pranolol can 'be added if required. ease. Am I Obstet Gynecol 53: 372, 26. MINKOWITZ 5, SOLOWAY HR. HALL Should blood pressure control still 1947 JE, et al: Fatal hemorrhagic 9. SCHEWITZ U: Hypertension and renal pancrea- not be achieved, therapy with agents disease in pregnancy. Med Clin North titis following chlorothiazide adminis- such as reserpine, guanethidine, do- Am 55: 47, 1971 tration in pregnancy. Obstet Gynecol nidine or propranolol can be con- 10. CHESLEY LC: Hypertensive disorders 24: 337, 1964 sidered; however, patients requiring in pregnancy, in Williams' Obstetrics, 27. RODRIGUEZ SU, LEIKIN SL, HILLER 14th ed, HELLMAN LM, PRITCHARD MC: Neonatal thrombocytopenia as- these medications should be admitted JA (eds), New York, Appleton- sociated with ante-partum administra- to hospital for bed rest and careful Century-Crofts, 1971, pp 685-748 tion of thiazide drugs. N Engi J Med monitoring. If accelerated hyperten- 11. KINCAID-SMITH P, BULLEN M, MILLS 270: 881, 1964 sion develops, the patient should be J: Prolonged use of methyldopa in 28. Hoechst Pharmaceutical Co: Lasix, admitted to hospital and the blood severe hypertension in pregnancy. Br manufacturer's insert, Hoechst, Somer- Med 1 1: 274, 1966 ville, NJ pressure should be controlled. Using 12. REDMAN CWG, BEILIN U, BONNAR 29. BRINKMAN CR, ASSALI NS: Utero- modern methods of maternal and J, et al: Fetal outcome in trial of placental hemodynamic response to fetal monitoring, the clinician should antihypertensive treatment in preg- anti-hypertensive drugs in hyperten- make a decision regarding early de- nancy. Lancet 2: 753, 1976 sive pregnant sheep, in Hypertension 13. ALTCHEK A: Renal biopsy and its in Pregnancy, 1st ed, LINDHEIMER livery on the basis of fetal maturity clinical correlation in toxemia of preg- MD, KATZ Al, ZUSPAN FR (eds), New and maternal and fetal stability. nancy. Circulation 30 (suppl 2): 43, York, Wiley, 1976, pp 363-72 Pregnancy in women with under- 1964 30. REED RL, CHENEY CB, FEARON RE, lying essential hypertension is not 14. CIBILS LA: The placenta and new- et al: Propranolol therapy throughout free of maternal or fetal risk, but born infant in hypertensive conditions. pregnancy: a case report. A nesth Am J Obstet Gynecol 118: 256, 1974 Anaig (CIeve) 53: 214, 1974 the frequency of complications is 15. HOWIE PW, PRENTICE CRM, Mc- significantly less today than the rates NICOL GP: Coagulation, fibrinolysis 31. GLADSTONE GR, HORDOF A, GER- in frequently quoted early papers. and platelet function in pre-eclampsia, SONY WM: Propranolol administra- essential hypertension and placental tion during pregnancy: effects on the With proper antihypertensive therapy insufficiency. I Obstet Gynaecol Br fetus. J Pediatr 86: 963, 1975 and aggressive maternal and fetal Commonw 78: 992, 1971 32. TURNSTALL ME: The effect of pro- monitoring, the maternal risk should 16. LANDESMAN R, HOLZE E, SCHERR L: pranolol on the onset of breathing at be small and the fetal outlook ex- Fetal mortality in essential hyperten- birth. Br J Anaesth 41: 792, 1969 cellent. Although pregnancy con- sion. Obstet Gynecol 6: 354, 1955 33. FREUND U, FRENCH W, CARLSON RW, 17. LEATHER HM, HUMPHREYS DM, et al: Hemodynamic and metabolic tinues to be relatively contra- BAKER P, et al: A controlled trial of studies of a case of toxemia of preg- indicated in women with essential hypotensive agents in hypertension in nancy. Am J Obstet Gynecol 127: hypertension who are older, have pregnancy. Lancet 2: 448, 1968 206, 1977 CMA JOURNAL/APRIL 22, 1978/VOL. 118 939 34. NAKAMURA J, RAux JF, BROWN EG, et al: Total lipids and the lecithin- sphingomyelin ratio of amniotic fluid: an antenatal test of lung immaturity? Am J Obstet Gynecol 113: 363, 1972 35. OSTERGARD DR, KUSHINSKY S: Uri- nary estriol as an indicator of fetal well-being. Obstet Gynecol 38: 74, 1971 36. KELLY AM, ENGLAND P, LORIMER JC, et al: An evaluation of human placental lactogen levels in hyperten- sion of pregnancy. Br J Obstet Gynae- ccl 82: 272, 1975 37. FREEMAN RK: The use of oxytocin challenge test for antepartum clinical evaluation of uteroplacental respira- tory function. 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CLINICAL NUTRITION. A Physiologic Ap- proach. Meredith Holloway Overton and Barbara P. Lukert. 171 pp. IlIust. Year Hygroton Book Medical Publishers, Inc., Chicago, (chiorthalidone) 1977. $11.85, paperbound. ISBN 0-8151- 5648-0 antihypertensive diuretic COGNITIVE AND EMOTIONAL DISTUR- BANCE IN THE ELDERLY. Clinical Issues. Edited by Carl Eisdorfer and Robert 0. with over Friedil. 169 pp. Illust. Year Book Medical Publishers, Inc., Chicago, 1977. $17.60. 15 years of clinical use ISBN 0-8151-3032-5 GYNECOLOGIC OPERATIONS. As Per- formed by Members of the Staff of the Woman's Hospital, St. Luke's Hospital Center, New York. Harold MM. Tovell and Leonard D. Dank. 321 pp. lIlust. Har- per & Row, Publishers, Inc., Hagerstown, Geigy 1978. Price not stated. ISBN 0-06-142553-2 Dorval, Qu.. HiDDEN CAUSES OF INJURY, PREVENT- H9S iBi ION AND CORRECTION, FOR RUNNING ATHLETES AND JOGGERS. John Jesse. 384 pp. Illust. The Athletic Press, Pasa- dena, 1977. $12.95. ISBN 0-87095-065-7 Complete prescribing information available on request G 8024 continued on page 953 940 CMA JOURNAL/APRIL 22, 1978/VOL. 118