Limits Of Normal Variation Research Articles

Early eruption of deciduous and permanent teeth: A case report

A family of three children with detailed records of eruption times and sequence is presented. Dental eruption, dental maturation, skeletal ossification age, height, and weight are compared to standards for chronologic age. Two of the children showed eruption patterns within the normal range. One child, a girl 7 years 11 months of age, displayed marked advancement of eruption of the deciduous and permanent dentitions outside the limits of normal variation. This child also displayed marked advancement in anterior vertical facial growth; she was of very short stature and on the light side in weight for her chronologic age and the skeletal age corresponding to her chronologic age. Otherwise, this child had the normal physical characteristics of a 7-year-old girl. Laboratory tests to detect hyperthyroidism proved negative. No etiologic cause for this extreme advancement in dental development was evident. Marked generalized early maturation and eruption of the dentition of this girl appears to be an idiopathic phenomenon.

Plasma oestriol concentration during normal pregnancy.

SummarySerial measurements were made of the concentration of plasma oestriol in normal pregnancy. The mean curve and limits of normal variation have been defined. The mean curve was analyzed and the correlations between various features of the pregnancy and plasma oestriol concentrations at particular stages of gestation were examined. Serial plasma oestriol concentrations seemed to give a better indication of feto‐placental function than serial urinary oestriol excretion values.

The Histamine-Eosinophil Test in Rheumatoid Arthritis and Rheumatic Fever

SummaryA study has been made of the reactions of rheumatoid arthritis and rheumatic fever patients (49 and 25 cases, respectively) in the histamine-eosinophil test (the effect of 0.5 mg. of histamine phosphate on the number of eosinophil cells in the blood as determined after 30 minutes). No differences in responses were noted between these groups and a control group (51 subjects). In all groups a tendency of the eosinophil number to decrease below the lower limit of normal variation following histamine injection was noted. Among rheumatic fever patients with high antistreptolysin-O titres marked reductions in the eosinophil numbers were observed in a larger proportion than among patients with low AST values.

Comparison of amniography and pelvic angiography in the diagnosis of hydatidiform mole.

Hydatidiform mole is a pathologic pregnancy which may present problems in diagnosis. The clinician is faced with a dilemma: he desires to make an early diagnosis but is fearful of interrupting a normal gestation. The purpose of this paper is to compare the findings of the combination of pelvic arteriography and amniography performed in patients with hydatidiform moles. Hydatidiform mole occurs with a frequency of 1 in 2,000 pregnancies in the United States. A slightly higher incidence is noted in the Mexican and Oriental populations. Its early diagnosis is desirable to allow early termination of the abnormal pregnancy and avoid the later complications of hemorrhage associated with spontaneous unattended evacuation, the development of subsequent cancer, or early toxemia. Heretofore, the diagnosis of molar pregnancy has been based on presumptive signs and symptoms such as severe hyperemesis, an early toxemia, persistent uterine spotting or bleeding, uterine enlargement beyond that expected for the gestational dates, abnormally high titers of chorionic gonadotropins, absence of fetal parts on palpation and absence of fetal structures on roentgen examination. Recently, Acosta-Sison (1) described the passage of a uterine sound through the cervix. He noted that if resistance is not felt at the level of the internal os, it is assumed that the normal amniotic sac is absent and the uterus is filled with vesicles which allow passage of the sound. The objections to all the listed signs, symptoms, and tests are their presumptive nature and their dependence generally on negative rather than positive findings. Of course, all of these may be falsely negative or positive—they may be indicative of early threatened abortion, multiple gestation, the limits of normal variation or, as in the case of absent fetal parts on x-ray studies, simply due to the early stage of gestation. What is most desirable is a procedure or test easily performed with readily available equipment, which will give a positive diagnostic result and offer little or no hazard to the mother or to a potentially normal and viable gestation. The technic of amniography was described by Menees et al. (7) in 1930 who employed the procedure for placental localization in near-term pregnancies. Bayan and Apelo (2) reported its value in the diagnosis of hydatidiform mole in 1957. McLain (6) in 1964 reported one case of hydatidiform mole studied by amniography in his series. Pelvic arteriography in the diagnosis of hydatidiform mole was described by Borell and Fernström (3) in 1961. They reported 5 cases in which pelvic angiography was part of the work-up. Material Four cases of hydatidiform mole were studied by both pelvic angiography and amniography prior to evacuation of the uterus. The basic technic of amniography varies little from that originally described by Menees and his co-workers.

The relationship of pulse pressure and diastolic pressure to systolic pressure in healthy subjects, 20–94 years of age

The relationship of systolic pressure to diastolic pressure and pulse pressure has been studied in more than 20,000 apparently healthy subjects ranging in age from 20 to 94 years, for the purpose of developing quantitative standards of normal pulse pressure throughout the range of blood pressure. Diastolic pressure and pulse pressure were found to vary linearly with the systolic pressure, and regression equations expressing this relationship have been presented. No significant sex difference was found. However, in both sexes, advancing age resulted in a widening of the pulse pressure and related lowering of the diastolic pressure at all levels of systolic pressure. Thus, at ages 20–64 years, diastolic pressure increases about 4 mm.Hg and pulse pressure widens by 6 mm.Hg for each 10-mm.Hg rise in systolic pressure, whereas at ages 65–94 years, diastolic pressure increases 3 mm.Hg and pulse pressure widens by 7 mm.Hg for a comparable change in systolic pressure. Hence, the pulse pressure virtually quadruples when systolic pressure increases from 90 to 220 mm.Hg. Limits of normal variation have been presented. These quantitative standards should prove to be useful in the evaluation of cardiovascular diseases or hemodynamic abnormalities which affect the pulse pressure.

DIE AUSSCHEIDUNG DER 17-HYDROXY-20-OXO-20-METHYL-STEROIDE (21-DESOXYKETOLE) BEI GESUNDEN FRAUEN UND BEI FRAUEN MIT ANDROGENEN VERÄNDERUNGEN

ABSTRACT The urinary excretion of 17-hydroxy-20-oxo-20-methyl-steroids (21-deoxy-ketols) was estimated in various clinical conditions, using the method of Appleby & Norymberski. The following results were obtained: In healthy women, the excretion rate varies with age. Before puberty, the mean values are below 100 μg/d; they rise to 300 μg/d at 30 years, then they fall again to less than 100 μg/d at the menopause. The limits of normal variation between women of the same age are 60 and 180% of the mean excretion rate (fiducial limits calculated for P = 0.05). In congenital adrenocortical hyperplasia, the excretion is markedly higher than normal. During treatment with 100 mg of cortisone daily, the levels decrease within four days to less than 200 μg/d. The excretion is within the normal range – (a) in women with hirsutism and normal or slightly increased 17-ketosteroid excretion, associated or not with menstrual disorders, and (b) in cases of the Stein-Leventhal syndrome. In metabolic experiments with 17α-hydroxy-progesterone (50 to 100 mg injected intramuscularly during the menstrual cycle or after the menopause), 2.0–3.5% of the administered amount are recovered as urinary 21-deoxy-ketols. In practical importance, the method is similar to the estimation of pregnanetriol. The technique is described in detail. Its reliability is satisfactory, and it helps to simplify considerably the routine operation of steroid assays.

CHAPTER 7 HEART CATHETERIZATION

Summary1. Heart catheterization was performed before shunt operation for morbus caeruleus in 101 cases. Only in 42 of these was it possible to guide the catheter into the pulmonary artery in order to measure the pressure there. After operation 89 cases were studied by heart catheterization and in 44 cases the pulmonary artery pressure could be measured. The difficulties in reaching the pulmonary artery arose from the anomalous anatomy.2. In 15 cases pulmonary artery pressure could be compared before and after operation. Preoperatively the readings were normal or subnormal. Postoperatively there was statistically significant increase in the systolic and diastolic pressures. These were still within the limits of normal, however, except in 2 patients with slight to moderate hypertension, probably as the result of the increased flow to the pulmonary artery via the anastomosis.3. Among the postoperatively catheterized patients without comparable preoperative measurements, 2 had slight pulmonary hypertension; the systolic pressure did not exceed 40 mm Hg. Comparison between all the preoperative and all the postoperative readings of pulmonary artery pressure showed probable increase of the mean systolic and diastolic pressures, but the difference was not statistically significant. The normal limits of variation were not exceeded. Only one patient with hypertension and clinical signs of functioning anastomosis revealed appreciable cardiac enlargement in the roentgenograms.4. The systemic arterial oxygen saturation could be compared preoperatively and postoperatively in 69 cases. The saturation tended to be distinctly higher after operation, and in some cases the readings during rest were within the limits of normal variation.5. Polyglobulia was found to be related to systemic arterial oxygen saturation and diminished as the oxygen saturation increased.

Tissue isodose curves for beta surface applicators.

Beta-emitting surface applicators have been in clinical use for many years. The inconsistencies between physical dosage and clinical results have been such, however, that it has, for practical purposes, fallen upon each clinician to evaluate his own applicator on the basis of his personal experience. Poor correlation has resulted when attempts were made to compare results from one applicator with those from another, or from one clinic with those from another. Hughes (1), impressed by these difficulties, asked the question, “How can an ophthalmologist or radiologist be certain of the clinical effect to be expected from a specific applicator?” The strontium-yttrium-90 applicators are in common usage today in many clinics and offices. The half-life of strontium 90 is given as twenty years (2). In some cases of recalibration of these applicators, the dose rate was found to have decreased by as much as 70 per cent of one half-life in one year. This rapid change in the strength of an applicator with a long half-life can be explained only by inconsistencies in the methods of calibration. Yet the same methods of calibration are in use today. In clinical medicine we must accept occasional inconsistencies in therapeutic results because of normal biological variation. However, we have felt, as have others, that the lack of consistency of results in the case of topical beta therapy has been significantly beyond the limits of normal variation. It is evident that a fundamental error exists, either in the hypothesis, in the technic, or in the interpretation of the experimental data used in support of the hypothesis. In an effort to clarify the basic concepts of the dose delivered to tissue by a surface beta applicator, we must first understand the steep gradient of absorption of particulate radiation. Any surface beta applicator has a finite area, usually 1 sq. cm. or less, with a uniform distribution of radioactive material over its surface. Assume that such a beta applicator, emitting 100,-000 beta particles each second, is placed in contact with an area of tissue. Since these particles may possess energies ranging from a few hundred electron volts up to a maximum value of several million electron volts, it is evident that they will penetrate to significantly different depths in the tissue. If we assume that 100 per cent strike the surface, 40 per cent penetrate to a depth of 1 mm., 16 per cent to a depth of 2 mm., etc., the resulting density of the radiation within the tissue would be as shown in Table 1. A practical example is shown in Figure 1. This figure demonstrates a hypothetical distribution of beta radiation density within a 1.0 c.c. block of tissue under the applicator. It is apparent that 100 per cent of the radiation is absorbed within the 1.0 c.c. of tissue.

The Histamine-Eosinophil Test in Rheumatoid Arthritis and Rheumatic Fever

SummaryA study has been made of the reactions of rheumatoid arthritis and rheumatic fever patients (49 and 25 cases, respectively) in the histamine-eosinophil test (the effect of 0.5 mg. of histamine phosphate on the number of eosinophil cells in the blood as determined after 30 minutes). No differences in responses were noted between these groups and a control group (51 subjects). In all groups a tendency of the eosinophil number to decrease below the lower limit of normal variation following histamine injection was noted. Among rheumatic fever patients with high antistreptolysin-O titres marked reductions in the eosinophil numbers were observed in a larger proportion than among patients with low AST values.

GROWTH IN HEAD WIDTH DURING THE FIRST TWELVE YEARS OF LIFE

This paper brings together the research findings on biparietal diameter from more than 50 investigations. It constitutes a synthesis of present knowledge pertaining to the head breadth of physically normal, North American infants and children. There are sections on the following topics: methodologic considerations, means for head width, variability in head width, findings from longitudinal data, and the relation of head width to other variables. Included in the section on variability is a table of norms and comments on its clinical use. Representative generalizations are: 1. The average North American white child attains 30% of adult head width by the middle of prenatal life, 60% by birth, 80% by 6 postnatal months, 90% by 3 years and 95% by 9 years. 2. Throughout the period from birth to 12 years, the 2 sexes differ systematically: head width distributions for North American white girls have slightly lower means and smaller standard deviations than comparable distributions for boys. 3. At 1 year of age, the limits of normal variation in head width are 11.4 cm. and 14.8 cm. for North American white boys, 11.1 cm. and 14.3 cm. for North American white girls. The normal limits at age 10 years are 12.9 cm. and 16.3 cm. for boys, 12.7 cm. and 15.9 cm. for girls. 4. North American Negro school children have narrower heads than North American white school children, and North American Japanese school children wider heads than North American white school children. The mean biparietal diameter of children of Mexican descent approximates that of American Negro children. 5. The association between width of head and length of head is low—of the order r = .25. A similarly low relationship exists between width of head and width of hips, but the relationship between width of head and width of face is appreciably higher.

BASAL BLOOD PRESSURE AND PULSE RATE IN ADOLESCENTS

Although measurements of the blood pressures of large populations of normal adults have been reported and the limits of normal variation have been fairly well established,¹relatively few measurements have been made for developing adolescents.²Pulse rates of untold thousands of high school children have been counted under unknown conditions of rest or exercise, but the information available on changes in the basal pulse rate with age during the adolescent period is scantly.³This report presents the results of repeated measurements of pulse rate and blood pressure taken at intervals of six months for the same persons (children aged 11.5 to 17.5 years) under basal conditions over a period of six years. <h3>SUBJECTS AND PROCEDURE</h3> The subjects for the cumulative study were 50 girls and 50 boys, chosen for the University of California Adolescent Growth Study from five elementary schools of Oakland, Calif. Since repeated testing of

The Bone Marrow in the Five-Day Treatment of Syphilis

SummaryThe intensive arsenical therapy used in the 5-day treatment of syphilis produces no demonstrable effect on the bone marrow of patients who have no individual idiosyncrasy to arsenical drugs. Cases of primary and secondary syphilis in which there is no change in the peripheral blood picture have a distribution of cell types in the bone marrow which is within the normal limits of variation.

Blood Sugar, Insulin, and Dextrose Tolerance in Albino Rat Treated with Carbon Monoxide

Conclusions1. Acute carbon monoxide asphyxia raises the blood sugar in direct proportion to the percentage of COHb induced. 2. Repeated exposure to carbon monoxide seems not to change the insulin tolerance significantly but to reduce the dextrose tolerance below the limits of normal variation. It reduces the fasting blood sugar 6-8 mg below that of untreated litter mates.

The Electroencephalogram of Schizophrenic Patients During Administration of Vitamin B1

Recent studies suggest that a deficient oxygen metabolism is present in schizophrenia. Increasing the rate of oxygen consumption in schizophrenics by means of thyroid and dinitrophenol has resulted in some clinical improvement. Since vitamin B1 is known to influence oxygen consumption of the brain, is seemed desirable to investigate its effect on the schizophrenic psychosis. The results of this study by Dr. L. H. Chase have been published elsewhere. The present report has to do with the electroencephalograms recorded during the major investigation. It has been found previously that thyroid and dinitrophenol increase the frequency of the “alpha” rhythm of the electroencephalograms. If vitamin B1 had the same effect, more direct evidence would be at hand to decide whether the medication influenced the metabolism of the brain. Five schizophrenic patients were given 100 mg of synthetic crystalline vitamin B1 daily for a period of 6 to 9 weeks. The medication was given orally except for the last 2 weeks, when it was administered intravenously. Weekly electroencephalograms were obtained from each patient for 3 weeks prior to medication, during medication and for 3 weeks after discontinuation of vitamin B1. Small, lead disc-electrodes were placed over the occipital lobes, and potentials recorded with reference to a pair of earthed leads on the mastoid processes. Two Grass amplifiers and ink-writing undu-lators were employed. The “alpha” frequency remained within normal limits of variation throughout the medication and post-medication periods. Likewise the amount of “alpha” activity (percent time alpha) did not vary more during medication than it did before or after vitamin B1 administration. Vitamin B1 administration has no observable influence on brain potentials from normal pigeons, but does have an appreciable effect in avitaminotic pigeons.

Urine of Pregnancy and Tumor Growth (Sarcoma 180)

Introduction This report concerns the fractionation of urine of pregnancy and the influence of two fractions upon the growth of sarcoma 180. The one fraction, containing a high prolan content, is tolerated by mice in a total dose corresponding to 3000 RE prolan units per mouse, produces no local indurations, affects neither caloric consumption nor body weight, and does not retard tumor growth. The other fraction, with a negligible prolan content, produces no local reactions, effects a loss in body weight, a decrease in caloric consumption, and a retardation in tumor growth. The results are interpreted as definitely establishing that prolan itself does not affect tumor growth, but that some other substances in urine of pregnancy cause tumor growth retardation by restricting caloric consumption and decreasing body metabolism. The literature leading up to these experiments has been reviewed previously (1). Experimental Standardization of Prolan: The prolan was standardized according to the method of Bischoff and Long (2). The prolan of the Winthrop Chemical Company is a German product and has been assayed by us (3). Ten German units prolan produced ovaries weighing 25 mg.; 10 of our units produced ovaries weighing 24 ± 2 mg. The agreement is within the limits of normal variation. It may therefore be assumed that our prolan unit approximated very closely the Zondek RE unit.

ERYTHROCYTE, HEMOGLOBIN, CELL VOLUME AND COLOR, VOLUME AND SATURATION INDEX STANDARDS FOR NORMAL CHILDREN OF SCHOOL AGE

So few are the reliable observations of the hemoglobin content of the blood during infancy and childhood that it would seem unwise to make a more precise statement concerning the average values and the normal limits of variation for the different age groups.... The data concerning red cell counts during infancy and childhood are so meager and so conflicting that no final statements can be made concerning the average values for the age periods nor the normal limits of variation.... The important values are not the averages, but the average limits of variation. It is just these which are particularly uncertain. This quotation from the report of the White House Conference on Child Health and Nutrition1indicates clearly the need for the study of normal hematologic standards in children. To help fill this need we have determined the red cell count, hemoglobin content and erythrocyte volume and have calculated

A method of establishing the probable limits of normal variation in the weight of organs

A method of establishing the probable limits of normal variation in the weight of organs

A study of child care in the first two years of life

Summary<ul><li>1.Fifty-nine children were studied at a Well Baby Conference organized by the Visiting Nurse Association in Hamden, Connecticut, with a desire to determine, first, methods of child care actually in operation; second, to define problems in management encountered by the mothers; and third, to arrive at conclusions with respect to the function fulfilled by a psychologist in such a conference. The group studied was a little above the average with respect to intelligence and economic level.</li><li>2.On the whole, methods of child care were encouragingly good, indicating that education in this field is making headway. It was increasingly apparent, however, that individual differences in infants (with respect, for instance, to food and sleep requirements) are too little stressed in the literature and in common parlance, with resultant undue anxiety on the part of those mothers whose infants deviate most from the accepted standards, even though such deviations fall within normal limits of variation. Reassurance was often necessary to the effect that even marked deviations could be considered as characteristic of a given child and did not constitute a threat to his general well-being.</li><li>3.A very few instances of most of the problems of management recorded in the literature were encountered in the course of the study. Of the forty-six children studied more than once, twenty-seven presented practically no problems, thirteen presented a succession of transient minor problems, six evidenced persistent difficulties. The prognosis with respect to ultimate adjustment was thought to be good for thirty-three of these forty-six children, questionable for nine, and poor for only two of them.</li><li>4.The existence of a preliminary period of difficult adjustment in the first two or three months of life has also been insufficiently emphasized in the literature. That the child needs time to adjust to rhythmic conditions of living and the mother, in her weak and emotional state, to her new responsibilities was repeatedly evidenced in the course of this study. The importance of sympathetic supervision and advice during this period cannot be overemphasized.</li><li>5.The situation with respect to the function of a psychologist in a Well Baby Conference defined itself as follows:<li>a.The way in which appointments were kept indicated that the mothers were very much interested in the information which the psychologist had to give them with respect to the infant's increment of mental growth.</li><li>b.Many of the suggestions made by the psychologist failed to be incorporated in the mother's program of child care until her own practical experience emphasized the need. The fact that suggestions respecting physical care were eagerly sought for and immediately put into practice, while suggestions regarding care from the psychologic standpoint were seldom sought, indicates that education in this field lags far behind that in the physical field. Further community education with respect to the type of question a psychologist is equipped to answer is necessary before such an individual in such a situation can be of maximum usefulness.</li><li>6.In the last analysis the mother's attitudes in child care situations are of first importance in determining the child's behavior. Not only must she be intellectually receptive to current concepts of child care, but also she must be so constituted with respect to temperament and so adjusted in her own emotional life that she can put her intellectual concepts into practice if she is to be successful in the management of her child.</li></li></ul>

THE INSENSIBLE PERSPIRATION IN INFANCY AND IN CHILDHOOD

Preliminary studies 1 demonstrated the constancy of basal measurements of the insensible perspiration in infants by the method of weighing under standard conditions. This demonstration of constancy and the absence of published basal figures led to the present study of a comparatively large and representative group of infants in an attempt to establish basal standards and normal limits of variation for this measurement in these subjects analogous to the well known standards at present available for their basal metabolism. The composition of insensible perspiration, 2 the apparatus and technic of measurements and the sources of error were fully considered in the previous paper. 1 That study established the reliability of measurements with the balance and showed that with careful technic the experimental error of the method was probably less than 10 per cent. The standard conditions that gave basal measurements in the previous study were employed in the present investigation.

EFFECT OF EXPERIMENTAL PYLORIC STENOSIS ON GASTRIC SECRETION

An increase above the normal average in the acidity of the gastric contents is observed in various conditions associated with pyloric obstruction in man. This condition is referred to as hypersecretion and hyperacidity. In most cases, however, the amount of acidity, although greater than the normal average, is within the limits of normal variation. Therefore, in the absence of a knowledge of the acidity of the gastric contents prior to the onset of the disease causing the pyloric obstruction, it may be argued that the acidity found is normal. Also, since there is usually a gastric retention in pyloric obstruction due to functional or organic disturbances, it is probable that a hypernormal acidity may be due to a retention of a normal amount of gastric secretion, and therefore is only relative. Even if hypernormal secretion did occur, one would not be able to state whether it was due to the