for detection of metabolic products of isoniazid in urine. Am Rev Respir Dis 106: 923, 1972 13. JORGENSEN HE, WIETH JO: Dialysable poisons. Haemodialysis in the treatment of acute poisoning. Lancet 1: 81, 1963

14. MAHER JF, SCHREINER GE: The dialysis of poisons and drugs. Trans Am Soc Artif Intern Organs 13: 369, 1967 15. Cocco AE, PAZOUREK U: Hazards to health. Acute isoniazid intoxication - management by peritoneal dialysis. N Engi J Med 269: 852, 1963

16. AAcK R, KISSANE J: Generalized seizures following isoniazid therapy for tuberculosis in a patient with uremia. Am J Med 53: 765, 1972 17. KATZ BE, CARVER MW: Acute poisoning with isoniazid treated by exchange transfusion. Pediatrics 18: 72, 1956

Normal blood pressure in offspring of persons with essential hypertension B.S. KAPLAN,* MB, B CH, FCP (sA); H. Fox,f MD, CM; E. SEIDMAN,* B Sc; K.N. DRUMMOND,§ MD, CM, FRCP[C]

Essential hypertension used to be considered less common in children than hypertension secondary to a demonstrable cause.1 Now, however, essential hypertension is diagnosed much more frequently,2'3 often as a result of screening . These programs are not without problems,7 which include induction of anxiety, false-positive results, invasion of privacy, expense and low yield.6 Since familial aggregation of blood pressure values has been shown in childhood,8'9 we considered it worth while to screen the children of persons with essential hypertension to see whether this approach would lead to a higher rate of detection of essential hypertension in the children. Methods Accepted definitions of hypertension are systolic or diastolic readings, or both, consistently above the 95th percentiles for age and sex.3'1 We used the normal values for blood pressure in children derived from several sources.2'11 Persons with essential hypertenFrom the department of nephrology, McGill University-Montreal Children's Hospital Research Institute *Assistant director, department of nephrology, Montreal Children's Hospital; associate professor, department of pediatrics, McGill University tRecipient of 1974 summer bursary, McGill University .Recipient of 1975 summer bursary, McGill University §Director, department of nephrology, and physician-in-chief, Montreal Children's Hospital; professor and chairman, department of pediatrics, McGill University Reprint requests to: Dr. B.S. Kaplan, Department of nephrology, Montreal Children's Hospital, 2300 Tupper St., Montreal, PQ H3H 1P3

sion were selected from the hypertension clinic of Montreal General Hospital if they had children under 22½ years of age. Essential hypertension was diagnosed in the parents on the basis of sustained hypertension, normal urinalysis results, normal concentrations of blood urea nitrogen, serum creatinine and electrolytes and urinary vanillylmandelic acid, and normal findings from intravenous urography. To obtain informed consent for measurement of the child's blood pressure the nature of the proposed family study was explained carefully to the parent or to the child when applicable. Twenty-nine families were studied. During the summer of 1974 and again in 1975 each family was visited at home by a medical student, usually in the evening after dinner. A family history of hypertension was sought. The child rested recumbent for 15 minutes, then lay supine while the blood pressure was measured three times in each arm with a mercury sphygmomanometer. In each individual the largest possible blood pressure cuff was used that is, the cuff that covered as much of the arm as possible while permitting reliable auscultation at the antecubital fossa. This was done to avoid spuriously high readings.12'13 The systolic blood pressure was taken as the pressure at which the first Korotkoff sound appeared; the diastolic pressure was taken as the pressure at which the sounds became muffled.12'13

racial, ethnic and religious composition reflected that of the population of Montreal. In 14 families the father and in 12 the mother had hypertension; in 3 families both parents were affected. The fathers' ages were 35 to 64 years and the mothers' 34 to 58 years. On the average hypertension had first been detected after 34 years of age in the men and after 20 years of age in the women. A family history of hypertension was given by 22 of the 32 affected parents. None of the children were considered to be hypertensive when their blood pressures were compared with normal values for age.10 Most of the mean systolic and diastolic measurements (Figs. 1 and 2 respectively) were scattered about the 50th percentile and, although there appeared to be a gradual increase in values with age, no values were above the 95th percentile.

Discussion

The reported frequency of persistent essential hypertension in children varies from 1.2% to 11 % .1,1,4.14.16 Before making the diagnosis of persistent essential hypertension in a child one must take many factors into account, including the definition of significant hypertension, the differentiation of essential and secondary hypertension, and the age, sex and race of the child. Furthermore, it is important to use the correct size of cuff and inflatable bladder and to pay careful attention to the technique Results of measurement. The setting in which Twenty-nine families with 94 chil- the pressure is recorded is also imdren, 47 boys and 47 girls, aged 2½ portant; it is possible that different to 22½ years were studied. Six chil- measurements can be expected dren were studied only once. The depending on whether the child is CMA JOURNAL/JUNE 10, 1978/VOL. 118 1415

examined at school, in a hospital emergency room, doctor's office or shopping mall, or in his or her home. Careful consideration of these factors led us to focus our attention on a selected group of children who seemed to be at risk for essential hypertension.17 This approach was based on the demonstration of higher blood pressures in family members of persons with hypertension than in control subjects with normal meas-

urements,17"8 on the finding of familial aggregation of blood pressure8 and on the demonstration of genetic factors in the occurrence of hypertension.9'19 None of the children in our group had persistent essential hypertension, although a few had values at the upper limit of normal. The absence of hypertension was unexpected since we thought that these children were at high risk. Our findings are similar

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to those from a study at Aleut children, one or both of whose parents were hypertensive; none of the offspring had hypertension, although 32% had potential hypertension, which was defined as systolic blood pressures above the 80% confidence level.20 There are several possible explanations for our findings. The sample may have been too small, but this group was at high risk and it was expected that the frequency of persistent essential hypertension would be equal to or greater than that reported by others. Observer error, in our judgement, was unlikely, for care was taken in the training of each observer; the student who obtained the measurements in the second summer was unaware of the values obtained the previous year, yet his results were virtually identical to those recorded a year earlier. Measurement in the child's home may have contributed to the normal values that were recorded. Because the 95% confidence limit of the proportion of children with hypertension in this group was 0% to 4% there is a 95% chance that the true proportion was 3.62% or less.21 However, despite this statistical conclusion, it appears that essential hypertension may not be as common in children as some studies have indicated, and that large-scale screening programs to detect essential hypertension in children may not be warranted. References 1. Loaom JMH: Hypertension in children and adolescents. I. Causes and diagnostic studies. J Pediatr 74: 331, 1969 2. Loi.iun S: Blood pressure standards for normal children as determined under office conditions. Clin Pediatr (Phila) 7: 400, 1968 3. LONDE S, GoLDIUNG D: Hypertension in children. Am Heart J 84: 1, 1972 4. HEYDEN S, BARTEL AG, HAMES CG,

et al: Elevated blood pressure levels in adolescents, Evans County, Georgia. Seven year follow-up of 30 patients and 30 controls. JAMA 209: 1683, 1969 5. KILCOYNE MM: Adolescent hypertension. Am J Med 58: 735, 1975 6. SILVERBERO DS, V. Nosm.m C, JUcKLI B, et al: Screening for hypertension in a high school population. Can Med Assoc 1 113: 103, 1975 7. ALDERMAN MH, YANO K: How prevalence of hypertension varies as diagnostic criteria change. Am I Med Sci 271: 343, 1976

Ludiomil® .x.de 8. ZINNER SH, LEvY PS, KASS EH: Familial aggregation of blood pressure in childhood. N Engi J Med 284: 401, 1971 9. BIRON P, MONGEAU J-G, BERTRAND

D: Familial aggregation of blood pressure in childhood is hereditary. Pediatrics 54: 659, 1974 10. MITCHELL SC, BLOUNT SG JR, BLU-

MENTHAL 5, et al: The pediatrician and hypertension. Pediatrics 56: 3, 1975 11. BIRON P, MONGEAU J-G, BERTRAND D: Blood pressure values in 1116 French-Canadian children. Can Med

Assoc 1 114: 432, 1976 12. KIRKENDALL WM, BURTON AC, Ep-

STEIN FH, et al: Recommendations

for human blood pressure determinations by sphygmomanometers. Circulation 36: 980, 1967 13. STEINFELD L, ALEXANDER H, COHEN ML: Updating sphygmomanometry.

Am J Cardiol 33: 107, 1974 14. MASLAND RP JR, HEALD FP JR, GOOD-

ALE WT, et al: Hypertensive vascular disease in adolescence. N Engi I Med

255: 894, 1956 15. KILCOYNE MM, RICHTER RW, ALSUP

PA: Adolescent hypertension: I. Detection and prevalence. Circulation 50:

758, 1974 16. DUnE 5K, KAPOOR S, RATNER H, et

al: Blood pressure studies in black children. Am I Dis Child 129: 1177,

1975 17. AYMAN D: Heredity in arteriolar (essential) hypertension; a clinical study of the blood pressure of 1524 members of 277 families. Arch Intern Med 53: 792, 1934 18. GEARING FR, CLARK EG, PERERA GA,

et al: Hypertension among relatives of hypertensives: progress report of a family study. Am J Public Health 52: 2058, 1962 19. MCILIIANY ML, SHAFFER JM, HINEs

EA: Heritability of blood pressure: an investigation of 200 pairs of twins using the cold pressor test. Johns Hopkins Med J 136: 57, 1975 20. TORREY EF, TORREY MS: Familial aggregation of blood pressures among Aleut children. Pediatrics 59: 633, 1977 21. DIEM K (ed): Documenta Geigy Scientific Tables, 6th ed, Geigy, Basel, 1962, p 98

BOOKS continued from page 1404 THE THYROID. A Fundamental and Clinical Text. 4th ed. Edited by Sidney C. Werner and Sidney H. lngbar. 1047 pp. Illust. Harper & Row, Publishers, Inc., Hagerstown, 1978. $52.50. ISBN 0-06142678-4 TRENDS IN FERTILITY IN THE UNITED STATES. Data from the National Vital Statistics System. Series 21, No. 28. National Center for Health Statistics. 41 pp. Illust. U.S. Department of Health, Education, and Welfare, Public Health Service, Hyattsville, 1977. Price not stated, paperbound. DHEW publ no (HRA) 78-1906

Brief prescribing information. Indications Endogenous depressive illness, including the depressed phase of manic-depressive illness (bipolar depression) and involutional melancholia. Selected patients suffering severe depressive neurosis. Contraindications Ludiomil (maprotiline) should not be used concomitantly with monoamine oxidase inhibitors; at least fourteen days should elapse between discontinuing one of the interacting drugs and replacing it with the other. Ludiomil is contraindicated in patients with existing severe hepatic or renal damage, a history of severe blood dyscrasias, narrow angle glaucoma, convulsive disorders and during the acute recovery phase following myocardial infarction. Not recommended for use in children. Use in Pregnancy Sate use of Ludiomil during pregnancy and lactation has not been establishe therefore, it should not be administered to women of childbearing potential or nursing mothers unless the benefits outweigh the possible hazards. Warnings Extreme caution should be used when Ludiomil (maprotiline) is given to patients with known cardiovascular disease including a history of myocardial infarction, arrhythmias andlor lachemic heart disease. Use with caution in hyperthyroid patients or those on thyroid medication, and in patients with a history of urinary retention, particularly in the presence of prostatic hypertrophy. Close supervision and careful adjustment of dosage is required when administering Ludiomil with anticholinergic or sympathomimetic drugs. Patients requiring concomitant treatment for hypertension should not be given antihypertensives of the adrenergic-neurone inhibitor type, such as guanethidine. Activation of psychosis in schizophrenic patients, hypomanic or manic episodes in patients with cyclic disorders have occurred with tricyclic antidepressants. The use of an antipsychotic drug in these latter two conditions is recommended should they occur in the course of Ludiomil administration. Precautions Seriously depressed patients must be carefully supervised due to the possibility of suicide. Patients should be warned that their responses to alcoholic beverages or other CNS depressanta may be exaggerated. Patients should also be cautioned against performing potentially dangerous tasks that require mental alertness and good physical coordination. Periodic blood cell counts and liver function tests are recommended with prolonged therapy. Prior to elective surgery, Ludiomil shou ldbe discontinued for as long a period as clinically feasible. Adverse reactions The following adverse reactions have been reported either with Ludiomil or the tricyclic antidepressant drugs: Neurological: numbness, tingling, paresthesias of extremities, incoordination, ataxia, tremors, peripheral neuropathy, extrapyramidal symptoms, seizures, alteration in EEG patterns, tinnitus. Behavioral: confusional states (especially in the elderly) with hallucinations, disorientation, delusions; anxiety, restlessness, agitation, insomnia and nightmares, hypomania, mania, exacerbation of psychosis, decrease in memory, feelings of unreality, weakness and fatigue, drowsiness, dizziness, urinary frequency. Autonomic: dry mouth and, rarely, associated sublingual adenitis; blurred vision, disturbances of accommodation, mydriasis; constipation; paralytic ileus; urinary retention, delayed micturition, dilation of the urinary tract, perspiration, flushing. Cardiovascular: hypotension, hypertension, congestive heart failure, tachycardia, palpitatlon, myocardial infarction, arrhythmias, heart block, stroke and syncope. Hematologic: bone marrow depression including agranulocytosis, eosinophilia, purpura and thrombocytopenia may occur as an idiosyncratic response. Leukocyte and differential counts should be performed in any patient who develops fever and sore throat during the therapy; the drug should be discontinued if there is evidence of pathological neutrophil depression. Gastrointestinal: nausea or vomiting, anorexia, epigastric distress, diarrhea, bitter taste, stomatitis, ab6ominal cramps, black tongue, dysphagia, increased salivation, altered liver function. Endocrine: gynecomastia in the male, breast enlargement and gaiactorrhea in the female, increased or decreased libido, impotence, testicular swelling, elevation or depression of blood sugar levels, weight gain or loss. Allergic or toxic: skin rash, petechiae, urticaria, itching, photosensitization (avoid excessive exposure to sunlight); edema (9enerai or of face and tongue); drug fever, obstructive laundice, nasal congestion. Dosape Adults Outpatients: initially 25 mg t.i.d., may be increased in increments of 25-50 mg to a maximum of 50 mg q.i.d. Hospital patients: initially 50 mg b.i.d. or t.i.d., may be increased in increments of 25-50mg to a maximum of 300 mg daily. Elderly patients: generally 25 mg t.i.d. or q.i.d. Maintenance: dosage may be gradually reduced to 75 mg daily or less. A single daily dose of 75 mg to 150 mg at bedtime can be given by virtue of the long half-life of Ludiomil. This would ensure better patient compliance and may obviate the need for hypnotics. Sup p lied Tablets containing maprotiline hydrochloride, film coated, slightly biconvex: 25 mg, light orange marked CIBA one side and DP on other; 50 mg, orange marked CIBA on one side and ER on other; 75 mg, coral, scored, marked CIBA on one side and FS on other. Bottles of 50 and 500 tablets. Product Monograph supplied on request. References 1. Trick, K.L.K.: Double-Blind Comparison of Maprotiline (Ludiomil0) with Amitriptyline in the Treatment of Depressive Illness. J. mt. Med. Research, Vol. 3, Suppl. 2,1975. Edited by J.E. Murphy, Cambridge Medical Publications Ltd., England. pp. 67-70 2. Mathur, GN.: A Double-Blind Comparative Clinical Trial of Maprotiline (Ludiomil*) and Amitriptyline. J. mt. Med. Research, Vol. 3, Suppl. 2, 1975. Edited by JE. Murphy, Cambrid9e Medical Publications Ltd., England. pp. 71-743. S,ngh, AN., Saxena, B,: Maprotiline (Ludiomil,* CIBA 34,276-BA) and Imipramine in Depressed Outpatients: A Double-Blind Clinical Study. Current Therapeutic Research, Vol. 19, No. 4, April, 1976.4. Product Monograph-Ludiomil*

see page 1346

(ferrous sulfate-folio acid)

hematinic with folic acid indications

Prophylaxis of iron and folio acid deficiencies and treatment of megaloblastic anemia, during pregnancy, puerperium and lactation.

Contraindications

Hemochromatosis, hemosiderosis and hemolytic anemia.

Warnings

Keep out of reach of children.

Adverse Reactions

The following adverse reactions have been reported: Nausea, diarrhea, constipation, vomiting, dizziness, abdominal pain, skin rash and headache.

PrecauUons

The use of folic acid in the treatment of pernicious (Addisonian) anemia, in which Vitamin B12 is deficient, may return the peripheral blood picture to normal while neurological manifestations remain progressive. Oral iron preparations may aggravate existing peptic ulcer, regional enteritis and ulcerative colitis. Iron, when given with tetracyclines, binds in equimolecular ration thus lowering the absorption of tetracyclines.

Dosage

Prophylaxis: One tablet daily throughout pregnancy, puerperium and lactation. To be swallowed whole at any time of the day regardless of meal times. Treatment of megaloblastic anemia: During pregnancy, puerperium and lactation; and in multiple pregnancy: two tablets, in a single dose, should be taken daily.

Suppiied

SLOW-Fe folic tablets have an off-white colour and are supplied in push-through foil packs of 30; available in units of 30 and 120 tablets.

References

1. Nutrition Canada National Survey A report by Nutrition Canada to the Department of National Health and Welfare, Ottawa, Information Canada, 1973. Reproduced by permission of Information Canada. 2. R. R. Streiff, MD, Folate Deficiency and Oral Contraceptives, Jama, Oct. 5, 1970, Vol. 21 4, No. 1.

CIBA DORVAL, ou.s.c H95 1 Bi

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