Biomedical subjects
A Prader
Publications and source records attributed to A Prader.
Longitudinal anthropometric measurements in patients with growth hormone deficiency. Effect of human growth hormone treatment.
The effect of human growth hormone (6IU/m2 twice weekly i.m.) on standing, sitting, and subischial leg height, on arm length, head circumference, fronto-occipital and biparietal head diameter, bi-iliac (pelvis) and bihumeral (shoulder) width, body weight, triceps and subscapular skinfold thickness, and upper arm and calf circumferences was studied longitudinally over a period of 2 years in 37 prepubertal growth hormone deficient patients (29 boys, 8 girls). Thirteen of them had isolated growth hormone deficiency, 18 combined defects with other anterior pituitary hormone deficiencies, and 6 had been operated for a craniopharyngioma. The most retarded height and length measurements were influenced most markedly by treatment in the fashion of a characteristic catch-up growth, while head circumference, which was less retarded initially, increased more slowly. With exception of craniopharyngioma patients, who became slightly eunuchoid, both proportions (sitting height versus subischial leg height) were not changed by treatment. The disproportions of shoulder and hip width (relatively wide pelvis, narrow shoulders before treatment) tended to be normalized. The results in patients with operated craniopharyngioma were not as good as in those with idiopathic growth hormone deficiency.
Transient rise in luteinizing hormone and follicle stimulating hormone secretion during puberty studied in 113 healthy girls with tall stature.
To establish normal values for the LRH test in females around the age of puberty, we had the opportunity to study 113 health girls with tall stature. Plasma LH and FSH levels were determined before and after a bolus injection of LRH (25 microgram/m2). Hormone results could not be correlated with chronological age, bone age, height, weight, or public hair stages. However hormone results showed significant differences when grouped according to breast development and menarche. There was a continuous rise of gonadotropin levels, particularly of basal and peak LH values, in parallel with breast maturation, and a remarkable fall in girls after menarche when tested during the first half of the menstrual cycle. It appears that a transient rise in gonadotropin secretion is essential for the maturation of ovarian function, which, in turn, switches pituitary-gonadal regulation from the pubertal tonic to the adult cyclic type.
Two types of male pseudohermaphroditism due to 17, 20-desmolase deficiency.
Three patients with male pseudohermaphroditism due to 17,20-desmolase deficiency were studied at a pubertal age. Patients 1 and 2 (first cousins, raised as males) had inter-sexual external genitalia, some spontaneous male pubertal development, some response of plasma testosterone to hCG, low plasma dehydroepiandrosterone, and pregnanetriolone (3 alpha, 17 alpha, 20 alpha-trihydroxypregnan-11-one) in urine. Patient 3 (unrelated, raised as a female) had female external genitalia, no spontaneous pubertal development, no response of plasma testosterone to hCG, normal plasma dehydroepiandrosterone, and no pregnanetriolone in urine. It is concluded that two types of 17,20-desmolase deficiency exist: one with an incomplete defect in both, the delta 4- and the delta 5-pathway (patients 1 and 2), and one with a complete defect in the delta 4-pathway only (patient 3).
Transient impairment or delay of urinary trihydroxypregnanone (THS) response to metyrapone in boys with delayed adolescence and in patients with isolated growth hormone deficiency.
Twenty three boys with delayed adolescence (age 15.7 +/- 2.0, bone age 12.4 +/- 2.1 years) were studied. Their cortisol response to insulin was normal. After oral metyrapone (500 mg/m2 by mouth) one to three consecutive 12 h urine samples were collected for analysis of THS. Thirty seven tests with 37 first, 21 second, and 11 third samples were carried out. The results could be divided into two main groups: 25 tests (group A) were subnormal in the first sample, 12 of them with a very weak (40 +/- 8 micrograms/m2/12 h) and 13 with an insufficient (191 +/- 16 micrograms/m2/12 h) THS response. Values in the second and third sample were higher, indicating a delayed response. In 12 tests (group B), the results were normal (1016 +/- 143 micrograms/M2/12 h) in the first and lower in the second and third samples. In three patients with repeated tests, there was improvement with increasing bone age. The THS-responses to metyrapone did not correlate with those of growth hormone, gonadotrophins, and TSH to stimuli. It is concluded that the THS-response to a single dose of metyrapone may be temporarily insufficient or delayed in delayed adolescence. We interpret this finding as showing transiently reduced or slow hypothalamic responsiveness.
Oto-spondylo-megaepiphyseal dysplasia (OSMED).
Four personal longitudinal observations and two cases from the literature are used to introduce the concept of oto-spondylo-megaepiphyseal dysplasia (OSMED). The condition may be recognized at birth. The main clinical findings are sensoneurinal deafness, enlarged 1st interphalangeal joints of the hands, relative short extremities with abnormally large knees and elbows but still normal total body length. In the second decade of life, backpain and decreased mobility of the joints may follow. 4/6 patients had a cleft palate. The diagnostic radiological findings are the big epiphyses combined with a moderate platyspondyly, most marked in the lower thoracic region. The occurrence of OSMED in two sisters suggests an autosomal-recessive transmission. No biochemical anomaly could be detected.
[Normal growth and disorders of growth in children and adolescents (author's transl)].
Normal growth and its variability are discussed on the basis of the new Zürich standard percentile charts. In the perinatal period boys grow faster than girls, presumably because of higher concentration of plasma testosterone. At the age of 6-7 years there is a modest midgrowth spurt, presumably caused by the increasing secretion of adrenal androgens (adrenarche). Just before puberty growth velocity reaches its lowest point. This is followed by the pubertal growth spurt with its peak at a mean age of 12 years in girls and 14 years in boys. This growth spurt is more marked in boys and is caused by the increasing secretion of gonadal steroids (gonadarche). Three or four years later growth ceases. Growth and bone maturation are closely related. In both the pubertal growth spurt and bone maturation girls are two years advanced compared to boys. From height and bone age a quite accurate estimation of the timing of puberty and of adult height can be made. Height and growth velocity are independent multifactorial variables. The majority of growth problems are caused by constitutional (familial) variants of height (familial short or tall stature) and of velocity of growth and maturation (familial acceleration or delay of growth and adolescence). The causes of growth disturbances of organic origin are chromosomal aberrations (e.g., Down syndrome), dysmorphology syndromes (e.g., Russell-Silver syndrome), endocrinopathies (e.g., hypopituitary dwarfism), chronic diseases (e.g., celiac disease), and bone dysplasias (e.g., achondroplasia).
Success, relapse and failure after intranasal LHRH treatment of cryptorchidism in 55 prepubertal boys.
Synthetic LHRH was given intranasally to 55 prepubertal boys with 67 undescended testes. After a 4-5 week period while receiving a daily dose of 1.2 mg complete testicular descent was seen in 24 testes. Follow-up over 6 to 24 months showed relapse in 4 boys who responded successfully to a second trial with LHRH. In boys with insufficient or no response to an initial trial further treatment with LHRH in 11 cases or HCG in 5 cases also was without effect. Surgical correction after unsuccessful LHRH treatment in 32 boys with 35 undescended testes showed anatomical abnormalities in 28 testes, mostly an open processus vaginalis with or without hernia. Because of its simple and painless administration and the absence of unwanted side effects, intranasal LHRH is well-suited as initial treatment of cryptorchidism, particularly in young children.
Anthropometric measurements in patients with growth hormone deficiency before treatment with human growth hormone.
In 74 children (52 males, 22 females) with growth hormone (GH) deficiency (30 cases with isolated GH-deficiency, two of them familial; 4 familial and one isolated case with tendency for formation of antibodies against hGH; 29 with other pituitary hormone defects; 10 craniopharyngiomas), various anthropometric measurements were analyzed before treatment with hGH. In all groups, standing height, sitting height, and subischial leg height were equally retarded, and bihumeral width was more retarded than biiliac width; the head was relatively large; fat tissue was increased with subscapular skinfolds being greater than triceps skinfolds, indicating relative obestiy of the trunk; muscle and/or bone mass was reduced. In isolated GH-deficiency, head shape was slightly scaphoid; in combined defects, it was round, and in craniopharyngioma cases, it was brachycephalic. It is concluded that antrhopometric measurements may help in differentiating the type of GH-deficiency.
Gonadotropin deficiency and cryptorchidism in three prepubertal brothers with congenital adrenal hypoplasia.
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Effect of intranasal LHRH therapy on plasma LH, FSH and testosterone, and relation to clinical results in prepubertal boys with cryptorchidism.
Synthetic LHRH (HOE 471) administered intranasally over a period of 4 weeks for treatment of uni- or bilateral cryptorchidism in nineteen otherwise healthy prepubertal boys led to increased basal and peak LH values and to markedly decreased peak FSH values in the i.v. LHRH test. Basal testosterone remained unchanged. Sixteen cryptorchid boys treated with placebo served as a control group. The reduced FSH response to i.v. LHRH could be due to induction of a gonadal feedback mechanism rather than pituitary depletion of FSH, in view of the favourable therapeutic effect and the increased LH secretion seen in some of our patients. Pretreatment LHRH tests were available in twenty successfully and in twenty-eight unsuccessfully treated boys. LH values were similar in both groups, whereas FSH peak values were significantly higher in boys who responded successfully to subsequent therapy. Testicular descent occurred most readily in boys with a large pool of easily releasable FSH and without a significant rise in testosterone (in contrast to HCG treatment). We suggest that FSH induces changes that potentiate the local action of testosterone.
Effects of high dose oestrogen and testosterone treatment in adolescents upon trabecular and compact bone measured by 125I computed tomography. A preliminary study.
125I Computed Tomography (CT) allows for the selective determination of trabecular and compact bone mineral parameters in the radius. Using this technique the effects of high dose oestrogen treatment in 11 tall girls, and of high dose testosterone treatment in 5 tall boys were monitored. In both groups trabecular bone density (TBD) increased steadily during treatment at a rate of about 1% per month. Also in both groups the compact bone mineral increased steadily. These results are compared with those from a cross sectional study on 49 normal children and 36 normal adults, in whom TBD was found to be independent of age and sex, so that the increases in TBD in both treatment groups can be attributed directly to the influence of the sex hormones. Since the compact bone mineral is higher in adults than in children it cannot yet be decided whether the increases seen in the treated patients are related to the sex hormone treatment, or reflect only the normal development of the bone during adolescence.
Hypophosphatemic vitamin D resistant rickets (phosphate diabetes): bone mineral problems studied by 125I-computed tomography and microradiography.
125I-computed tomography (CT) for the bone mineral analysis of the radius was performed on 9 children with vitamin D resistant hypophosphatemic rickets (VDRR) treated with vitamin D in pharmacological doses. Trabecular bone density was increased in 1 patient and normal in all others. The cortical width of the diaphysis of the radius was decreased, and the cross sectional area of the bone increased, but the total amount of compat bone mineral in the cross section was normal. Measurements of the second metacarpal bone on X-rays of the hand revealed similar findings. Microradiographic and histological examinations of the fibula on 9 different patients also treated with vitamin D showed grossly abnormal mineralization of bone tissue with a perilacunar mineral deficit. It is concluded, that the amount of compact bone and trabecular bone is not decreased in children with VDRR. The normal mineral content determined by CT and the impaired mineralization of the bone material examined by microradiography indicate an over-abundance of incompletely mineralized bone.
The incidence of congenital adrenal hyperplasia in Switzerland--a survey of patients born in 1960 to 1974.
The incidence of congenital adrenal hyperplasia (CAH) in Switzerland was calucated for patients born in 1960 to 1974. Information was obtained by means of questionnaires sent to all Pediatric Hospitals and Institutes of Pathology in Switzerland. The number of patients and the incidences of the different enzyme defects were: all cases 110 (1:13785 livebirths), 21-hydroxylase 98 (1:15472), 11 beta-hydroxylase 5 (1:303260), 3 beta-dehydrogenase 3 (1:505433). The incidence of females--which is 1:12098 for all cases and 1:13924 for 21-hydroxylase deficiency--presumably appropximates more exactly the real incidence, because of incomplete diagnosis in the male. Salt loss was observed in two thirds of patients with 21-hydroxylase deficiency. A more reliable estimate of the incidence of CAH could be obtained by neonatal screening programs with measurement of serum-17-hydroxyprogesterone.
[Weight, length and head circumference of the newborn infant and their relationship to maternal and infant factors. Standards for intrauterine growth].
Means, standard deviations and smoothed percentiles of fetal weight, length and head circumference at birth, and weight of the placenta between 26 and 44 weeks of gestation are presented. The data are based on 5136 single and 208 twin, live-born newborn infants delivered at the cantonal Hospital Winterthur between 1969 and 1974. The percentile curves differ considerably from those of the widely used "Lubchenco-Curves". Fetal weight correction factors for maternal weight, parity and sex of the child are given. Among the various maternal and infantile variables influencing fetal growth, gestational age and maternal weight were found to be the most significant ones affecting weight and length of the newborn. Parity and sex of the child were of moderate, maternal height and nationality of minor importance.
Evaluation of perinatal growth. Presentation of combined intra- and extrauterine growth standards for weight, length and head circumference.
The evaluation of perinatal growth requires different approaches depending on the chronological age of the infant. Basically, three periods of perinatal growth are to be distinguished: Intrauterine period: Growth during this period can be estimated by intrauterine growth standards representing fetal growth parameters at birth. Transitional period: Growth during the first 6 to 12 days of life is of transitional nature. It is characterized by large individual variations and does not follow any growth standards. Extrauterine period: After the 6th to 12th day of life growth rates are distinctly higher than those of intrauterine growth. Thus, intrauterine growth standards can not be applied to extrauterine growth, and separate growth standards are required to evaluate growth during this period. In this article combined intra- and extrauterine growth standards for weight, length and head circumference in boys and girls between 28 weeks of gestation and 8 weeks after term are presented. These growth standards are based on the Winterthur Newborn Study (1962-1974) and the Second Zurich Longitudinal Study (1974-1980).
Analysis of the growth spurt at age seven (mid-growth spurt).
A statistical analysis of the mid-growth spurt from the data of the First Zurich Longitudinal Study is presented. A small but significant mid-growth spurt was found in most height and length measurements and in some girth and width measurements, such as chest circumference, bihumeral and biiliac width. The mid-growth spurt seemed to be slightly more pronounced in boys than in girls. The peak of the mid-growth spurt occurred between 6.5 and 8.5 years. The height of the peak varied from 0.3 to 0.7 cm/year for the different measurements (estimated from the smoothed median velocity curves). In a peak-centered analysis a mid-growth spurt of standing height was observed in two thirds of the children. It occurred about one year earlier in girls than in boys, and averaged 1.4 cm/year. The data indicate that the mid-growth spurt is due to a transient increased growth rate of the bones, particularly the long bones, and possibly of fat and muscle tissue. In contrast to the growth spurt of the extremities, the spurt of the rump height is not a true growth phenomenon, but the result of a postural change occurring at about 6.5 years of age.
Loss and recovery of trabecular bone in the distal radius following fracture--immobilization of the upper limb in children.
Computed tomography of the human radius is performed using a special purpose scanning device which incorporates a radionuclide (125I) as radiation source. Parameters decribing the trabecular bone and the compact bone are determined at a distal and a diaphyseal measuring site respectively. Using this measurement technique changes in bone mineralization in the radius were studied in a group of 23 children following immobilization of an upper limb for fracture healing. An immobilization period of between three to six weeks resulted in a reduction of the relevant parameter value of up to 44% (mean 16%) in the distal part of the radius, whereas no significant change could be seen in the diaphyseal part of the same bone. Rapid remineralization of trabecular bone is indicated by the increase of the corresponding parameter value at a rate of up to several percent per week. However, in some of the patients studied complete normalization was not attained during the first six months following cast removal.