Untreated Siblings Research Articles

Regulation of neuron numbers in Xenopus laevis: effects of hormonal manipulation altering size at metamorphosis.

Xenopus laevis tadpoles reared in a 0.01% solution of 6-n-propyl-2-thiouracil (PTU) are blocked in their development at larval stage 54 but continue to increase in size. When released from the effects of PTU they metamorphose into frogs of sizes significantly larger than those of their untreated siblings. Using this size difference to examine the hypothesis that neuron numbers are matched to the size of their postsynaptic targets during neuronal cell death, we measured the following on stage 66 frogs metamorphosing from PTU-treated and untreated tadpoles: lumbar lateral motor column (L-LMC) motoneuron number and mean nuclear cross-sectional area; thoracic and lumbar dorsal root ganglion (DRG) cell number and mean nuclear cross-sectional area; and muscle fiber number in two representative thigh muscles. A few measurements of neuron number and cell size were also made on untreated and PTU-treated stage 54 tadpoles. The most striking correlations observed were not between peripheral size and neuron numbers but between peripheral size and neuron size. Motoneuron numbers were not increased in the PTU-treated animals, perhaps because the increase in peripheral size involved an increase in muscle fiber diameter rather than an increase in muscle fiber number. Thoracic DRG cell number, but not the sum of thoracic and lumbar DRG cell numbers, was increased. In general, our findings do not support the hypothesis that neuron numbers are matched to peripheral size by a process regulating the amount of cell death that occurs during metamorphic stages in Xenopus laevis.

Cerebroprotective effect of dexamethasone (DXM) in newborn piglets with experimental pneumothorax (EPT)

The effect of DXM treatment in newborn piglets with EPT was studied on 30 piglets. 20 animals were subjected to EPT (group A and B) and 10 piglets served as controls without EPT (group C). In the EPT animals 10 piglets were injected with 5 mg/bwkg sc DXM 4 hours prior to EPT (A). Each animal was paired with untreated sibling having the same EPT (B). In the EPT piglets 4 hours after the critical phase (as apnea appeared, MABP fell, the EPT was terminated) brain tissue water and Evans blue dye were determined. There was a highly significant difference between A and B piglets regarding the time necessary to the development of critical phase (A X=69.6±SD=27.5 vs B 28.7±10.1 minutes; p < 0.001). In the untreated EPT animals (B) the Evans blue content of the parietal cortex and cerebellum exceeded significantly the values obtained in DXM treated (A) and control piglets (C) - parietal cortex A 0.18±0.12, B 0.88±0.57, C 0.17±0.07; cerebellum A0.14±0.02, B 0.78±0.36, C 0.17±0.07 μg/dye/g wet tissue. The same phenomenon was observed regarding the water content of above brain regions, as well. In conclusion, DXM treatment increases the tolerance to hypoxia and prevents brain oedema in newborn piglets with EPT.

Parent‐child interaction training: Effects on family functioning

Parent‐child interaction training was designed for the treatment of disturbed preschool children and their families. This paper describes the treatment and its effects on seven referred children, their untreated siblings, and the psychological functioning of their parents using multiple process and outcome measures. High rates of attendance, home practice, cooperation, and satisfaction with treatment; significant pre‐ to post‐treatment changes in child and sibling behavior; and improvement in parental adjustment were found. Results suggest that one can alter parent‐child interaction patterns during a brief intervention so that family members are better able to interrelate and to deal effectively with problems.

Parent behavioral training to modify child noncompliance: Effects on untreated siblings

The purpose of the present study was twofold: (a) to examine changes in parent behavior toward an untreated sibling after parent behavioral training to modify a target child's noncompliance and (b) to examine changes in the untreated sibling's behavior. Eight clinic- referred children and their mothers served as the subjects. Parent training consisted of the use of a standardized clinic program to modify child noncompliance. The outcome measure was home observations of the parent and untreated child's interactions. The results indicated significant changes in both the parent's behavior and the untreated sibling's noncompliance.

Effect of long-term therapies with penicillin and sulfadiazine on Streptococcus mutans and lactobaccilli in dental plaque.

Plaque samples were obtained from 13 children receiving long-term therapy with benzathine penicillin for the prevention of rheumatic fever recurrences, 31 children receiving oral sulfadiazine for the same purpose, and 29 untreated siblings. The therapies were found to have no effect upon the proportions of Streptococcus mutans or lactobacilli in dental plaque, upon the percentage of children harboring the organisms, nor upon the susceptibility of the organisms to penicillin and sulfadiazine. Of the S. mutans strains tested, 97% had a minimal inhibitory concentration of penicillin G of less than 48 ng/ml and, of the lactobacillus strains tested, 96.8% had a minimal inhibitory concentration of less than 1,600 ng/ml. All strains of both organisms were profoundly resistant to sulfadiazine.

The effect of parental treatment with one child on an untreated sibling

Time-out for noncompliance and praise for compliance were used by a mother to modify the task completion times of her child. The effect on the task completion times of a sibling, who was present during treatment of his brother, was examined. Although the untreated child's behavior changed, these changes depended upon the similarity of the tasks assigned to the two children and the time at which the tasks were performed.

Familial congenital absence of adrenal glands; evaluation of glucocorticoid, mineralocorticoid, and estrogen metabolism in the perinatal period

The patient was the fourth of affected male siblings. Cortisol (1.3 micrograms per cent), cortisone (9.6), and corticosterone sulfate (0.1) concentrations were low in cord blood. The larger amount of cortisone may have originated from maternal cortisol. Aldosterone was undetectable in cord blood, indicating lack of fetal secretion or maternofetal transfer. Unexpectedly normal concentrations of 11-deoxycorticosterone (DOC) sulfate in cord serum could represent maternal transfer of DOC, with subsequent fetal sulfurylation. Low estrone and estradiol concentrations in maternal and cord serum were consistent with absence of the fetal adrenals. Despite the low levels of the steroids, the propositus had a normal lecithin-sphingomyelin ratio at 38 weeks' gestation. Circulatory insufficiency developed within half an hour after birth and responded to gluco- and mineralocorticoid therapy. The three untreated siblings died between 14 and 67 hours of age. It is evident that early recognition of this condition may be lifesaving.

Behavioral treatment in the home: Effects on an untreated sibling and long-term follow-up

Time out and differential reinforcement were employed to control the disruptivebehavior of a 3-year-old boy. Treatment was carried out in the home by the child's mother. The frequency of the boy's objectionable behavior varied according to the combined use of differential attention and time out. Differential attention alone was not effective in altering the problem behaviors. Similar changes in behavior were observed in the boy's 5-year-old sister although she was not considered a problem and no specific treatment plan had been designed to modify her responses. Follow-up observations over a 10-month period revealed that behavioral changes were maintained.

Responsiveness of bone to parathyroid extract in siblings with pseudohypoparathyroidism

Four siblings with pseudohypoparathyroidism (PHPT) were given parathyroid extract (PTE) for a period of 4 days. The responses of serum and urine calcium, inorganic phosphate, magnesium, and urinary hydroxyproline excretion to these injections were compared to those of five normal subjects and a patient with primary hypoparathyroidism. All patients with PHPT showed a characteristic impairment of the increase in serum calcium and urinary inorganic phosphate excretion. One of the patients, who was receiving 50,000 U daily of vitamin D, showed no greater response to PTE than her untreated siblings. All PHPT subjects exhibited an initial increase in hydroxyproline excretion that, unlike that of the normal subjects, was only transient and fell to only slightly above control levels by the fourth day of PTE injections. In this family, the results indicate that bone retained some of its sensitivity to parathyroid hormone but that the sensitivity was impaired and could not be corrected by administration of large doses of vitamin D.

PSYCHOLOGIC AND NEUROLOGIC STATUS OF DIET-TREATED PHENYLKETONURIC CHILDREN AND THEIR SIBLINGS

The neurologic status and intelligence of 8 phenylketonuric children treated with a phenylalanine-low diet were compared with that of 11 unaffected children and 3 untreated siblings. The mean intelligence of the treated children was significantly higher than that of their untreated siblings. This was true both for the two children given a special diet at 2 years of age and for those treated earlier, but the children treated before 6 months of age were significantly more intelligent than those treated at 2 years. The one child for whom treatment was begun at 1 year had an intelligence level within the range of the five who were treated earlier. Although intelligence was significantly higher in treated than in untreated children, and this was especially marked in the children treated early, all treated children were significantly less intelligent than their unaffected siblings. The loss in intelligence probably cannot be ascribed to poor chemical control, as treated children maintained phenylalanine levels within the normal range throughout treatment, with occasional brief exceptions. Neurologic findings paralleled the results of intelligence testing. There were no suggestive or positive findings among the unaffected children. Children treated early had some relatively minor findings, while children treated late and those who were untreated had a higher percentage and more marked signs of neurologic defect. Results of the present study considered together with results from other investigations, indicate that intelligence level, in phenylketonuric children, is a decelerating function of age. If this is true, the brain may be especially susceptible to damage in the first few weeks and months of life, and treatment should be instituted as early as possible.

Phenylketonuria. II. Results of treatment of infants and young children: A report of 10 cases

The results of dietary treatment of 10 infants and young children with phenylketonuria with a low phenylalanine diet (Lofenalac) from 6 months to 3 years (average 22 1/2 months per child) are presented. The group includes 4 babies started on the diet under 2 months of age, 1 at 8 months, and 4 from 1 to 3 years. The data include weights, heights, head circumferences, serum phenylalanine levels, electroencephalographic findings, personality and intelligence changes, and brief notes on individual diet control patterns. The following observations were made: 1.Initial changes in behavior paralleled the decrease in the serum level of phenylalanine, which usually was within the “therapeutic range” one to two weeks after starting the diet. The children became less irritable and less withdrawn, and their responsiveness and attention span were increased. 2.The 4 children who were placed on the diet prior to 2 months of age are developing within the normal and low-normal range. 3.The 6 children started on the diet from 8 months to 3 years of age have an average I.Q. of 72. 4.Ten normal siblings have an average I.Q. of 103, and 5 untreated siblings with phenylketonuria have an average I.Q. of 24. 5.The children generally had somewhat slow growth patterns but were well nourished for their heights. Little difficulty was experienced in giving the special diet. There were no complications of the treatment such as diarrhea, marked weight loss, or anemia. One young infant (H-2) had an unexplained severe rash for several months during early treatment. 6.Serum phenylalanine levels were usually maintained within a range of 1 and 8 mg. per 100 ml. 7.Six of the 10 children initially had abnormal electroencephalograms; 2 of the 4 normal electroencephalograms were on infants started on the diet while under 2 weeks of age. Of the latest tracings during the dietary treatment, only one of the 10 was abnormal. Conversion from abnormal to normal took place after 1 1/2 months to 2 1/3 years (average 11 1/2 months) on the diet. The results of dietary treatment of 10 infants and young children with phenylketonuria with a low phenylalanine diet (Lofenalac) from 6 months to 3 years (average 22 1/2 months per child) are presented. The group includes 4 babies started on the diet under 2 months of age, 1 at 8 months, and 4 from 1 to 3 years. The data include weights, heights, head circumferences, serum phenylalanine levels, electroencephalographic findings, personality and intelligence changes, and brief notes on individual diet control patterns. The following observations were made: 1.Initial changes in behavior paralleled the decrease in the serum level of phenylalanine, which usually was within the “therapeutic range” one to two weeks after starting the diet. The children became less irritable and less withdrawn, and their responsiveness and attention span were increased. 2.The 4 children who were placed on the diet prior to 2 months of age are developing within the normal and low-normal range. 3.The 6 children started on the diet from 8 months to 3 years of age have an average I.Q. of 72. 4.Ten normal siblings have an average I.Q. of 103, and 5 untreated siblings with phenylketonuria have an average I.Q. of 24. 5.The children generally had somewhat slow growth patterns but were well nourished for their heights. Little difficulty was experienced in giving the special diet. There were no complications of the treatment such as diarrhea, marked weight loss, or anemia. One young infant (H-2) had an unexplained severe rash for several months during early treatment. 6.Serum phenylalanine levels were usually maintained within a range of 1 and 8 mg. per 100 ml. 7.Six of the 10 children initially had abnormal electroencephalograms; 2 of the 4 normal electroencephalograms were on infants started on the diet while under 2 weeks of age. Of the latest tracings during the dietary treatment, only one of the 10 was abnormal. Conversion from abnormal to normal took place after 1 1/2 months to 2 1/3 years (average 11 1/2 months) on the diet.

Present health of children given x-ray treatment to the anterior mediastinum in infancy.

ARECENT SURVEY showed that the incidence of neoplasia in a group of children who had been treated with x-rays in infancy for enlargement of the thymus gland was higher than that in either their untreated siblings or in children of the same age in the population at large (1, 2). In particular, the number of cases of leukemia and thyroid cancer in the irradiated children far exceeded the number expected in a normal group of comparable size and age distribution. Although the findings are consistent with reports of an increased incidence of malignant disease, especially leukemia, in other human populations exposed to ionizing radiation (3-7), certain features of this study are sufficiently unusual to deserve further investigation. First, the doses of radiation were smaller than those formerly believed to be carcinogenic. Second, whereas the thyroid neoplasia and other cancers were found only in children exposed to comparatively high doses of x-rays (more than 200 r), leukemia sometimes occurred in children receiving less than 200 r. Third, because almost all children were selected for treatment on the basis of a diagnosis of thymic enlargement, it is impossible to differentiate the role of this factor from that of irradiation in the development of leukemia and other malignant diseases. The purpose of the present study is to obtain further information concerning the incidence of malignant disease in children treated with x-rays. The irradiated children in the series to be reported are of particular interest in that most of them had thymus glands of normal size. In this 3 per cent of the entire group. Although these children were usually asymptomatic, 80 per cent were treated with 200 to 450 r to the anterior mediastinum. In the course of the study, it was noted that signs and symptoms attributed to thymic enlargement never occurred in treated children who had enlarged thymus glands at birth. Since upper respiratory infections also seemed to be less prevalent in the treated children, it was decided to give all children born between June 1944 and May 1946 small doses of x-rays to the manubrial region. Ninety-five per cent of the 1,340 children so treated were given 150 r and the remainder received 75 to 100 r (Table I). A survey of these children, conducted by mail in 1948, reaching about half the total number, showed no apparent increase in either morbidity or mortality. The radiation factors used in treatment were: 140 kvp; filtration, 3 mm. Al; skin-target distance, 8 to 9 in.; port size, 4X4 cm.; port position, over the manubrium. Increments of 75-150 r were usually given at one- to two-day intervals. All children were treated within seven days after birth; children with illnesses not usually ascribed to thymic enlargement were excluded from the series. The method of interviewing parents of the treated children was the same as that used by Simpson and Hempelmann (2) except that the telephone was used wherever possible.

Carcinoma of the Thyroid in Children

In 1950 Duffy and Fitzgerald1reported a series of 28 children with thyroid carcinoma, of whom 9 had received irradiation to the thymic area in infancy. Hesitant to draw conclusions from these figures, Duffy and Fitzgerald did suggest that the possible relationship of thymic irradiation and thyroid carcinoma might be profitably explored. Although neither the report of Horn and Ravdin2in 1951 nor that of Warren and co-workers3in 1953 presented comparable statistics regarding the association of irradiation in infancy and later development of thyroid carcinoma, other studies have appeared which indicate that it is well worth while to pursue this line of inquiry. Simpson and her colleagues4reported that of 1400 children who had received thymic irradiation in infancy 6 subsequently developed thyroid carcinoma and 9 thyroid adenoma. In a control series of 1795 untreated siblings of the irradiated children, there were no cases of

Association of irradiation with cancer of the thyroid in children and adolescents.

The possibility that irradiation might be an etiological factor in carcinoma of the thyroid in children and adolescents was suggested by Duffy and Fitzgerald, 1 who found that 10 of 28 patients, 18 years of age or younger, seen at the Memorial Hospital had been subjected to irradiation to the thymus gland some time between the 4th and 16th month of life. Simpson, Hempelmann, and Fuller 2 studied the frequency of neoplasms in 1,400 of 1,722 children who had received x-ray therapy to the thymic area between 1926 and 1951 and found that the number of cases of thyroid cancer was markedly higher in the treated group than in either the untreated siblings or the general population. As short courses of low voltage x-rays have been widely used in children for benign conditions about the head, neck, and upper thorax other than thymic enlargement, a search of the literature was

Neoplasia in Children Treated with X-rays in Infancy for Thymic Enlargement

X-ray treatment of enlarged thymus in infants is no longer commonplace but is still practiced. The incidence of neoplastic diseases in 1,400 infants so treated between 1926 and 1951 was determined and compared with the incidence of neoplastic disease in 1,795 of their untreated siblings and with the expected incidence in the general population as calculated from vital statistics. Even taking limitations of the study into consideration the findings indicate that the radiation therapy of the thymus applied in infancy must be suspected as the cause for the greater incidence of neoplastic disease observed in the x-ray treated group; the majority of neoplasms occurred in those known to have received more than 200 r. Six individuals in the x-ray treated group developed cancer of the thyroid, none of the untreated siblings were so afflicted compared to the expected incidence, as calculated from data on the general population, of 0.08.

Neoplasia in children treated with X-rays in infancy for thymic enlargement.

Irradiation of enlarged thymus glands in infancy, a practice started by Friedlander in 1907 (1), was commonplace in this country from 1930 to 1945. Since many parents and physicians still firmly believe that thymic enlargement is a potentially dangerous condition, x-ray treatments continue to be given to young children with this diagnosis. Because of our interest in possible late sequelae of such x-ray therapy, we have undertaken a survey to determine the present health of 1,722 children treated between 1926 and 1951. Data on the 1,400 children traced to date show that the incidence of malignant neoplasia is high, acute leukemia and thyroid carcinoma being the most common forms of the disease. The high cancer rate in the treated groups is significantly above that in 1,795 untreated siblings and in the general population of the same age distribution. Although the medical literature contains numerous warnings about the possible dangers of the widespread and indiscriminate use of x-rays in the treatment of enlargement of the thymus gland, no concrete substantiating evidence has been presented. Duffy and Fitzgerald (2) suggested a possible association between thyroid cancer in childhood or adolescence and prior irradiation to the thymus gland. In 10 of their series of 28 cases of carcinoma of the thyroid there was a history of x-ray treatment. Two subsequent papers reviewing other series of childhood cancers of the thyroid do not report a history of irradiation (3, 4). Recently Dameshek (5) commented that in one month he had seen 3 children with leukemia who had received roentgen therapy to enlarged thymus glands. Previous attempts to follow children who had received x-ray therapy for thymic enlargement are limited in number and scope. In 1936, Polk and Rose (6) reported a study on 31 of 55 children treated before 1924. Only 18 of the children were less than eighteen months old when treated. One child died of leukemia, but this was only two weeks after treatment. In 1938, Kerley (7) noted that 27 patients were mentally and physically normal twenty-six weeks to sixteen years after irradiation. Conti and Patton (8) reported on a series of 7,400 consecutive newborn infants seen between 1937 and 1946. In the early part of their study, the 3 to 4 per cent of infants found to have roentgen evidence of thymic enlargement were given x-ray therapy whether or not they had symptoms. Later all infants received small doses of x-rays. As this appeared to increase the incidence of respiratory disease, prophylactic roentgen treatments were discontinued. These authors did not observe any cases of neoplasia in their follow-up study, which, however, included only one third of the cases and lasted only a few years for each child. Material Our 1,722 treated cases were taken from the records of three hospitals and from one pediatric and two radiological practices. The majority came from western New York and the rest from the State of Washington.

THE INFLUENCE OF HUMAN SERUM ALBUMIN ON EDEMA IN ERYTHROBLASTOSIS FETALIS

Summary Two cases of erythroblastosis fetalis complicated by severe generalizededema successfully treated with concentrated human serum albumin are reported. The first was one of twins, in which the untreated sibling died. In the second case, blood studies were done and it was found that the use of the serum albumin corrected an early fall in the blood protein level with subsequent elimination of the severe generalized edema. It is postulated that liver damage, frequently a feature in severe erythroblastosisfetalis, with a disturbed blood protein level was the causative mechanism of the edema, and that the serum albumin restored the level. Studies are now in progress further to elucidate these factors.

The influence of human serum albumin on edema in erythroblastosis fetalis

Two cases of erythroblastosis fetalis complicated by severe generalizededema successfully treated with concentrated human serum albumin are reported. The first was one of twins, in which the untreated sibling died. In the second case, blood studies were done and it was found that the use of the serum albumin corrected an early fall in the blood protein level with subsequent elimination of the severe generalized edema. It is postulated that liver damage, frequently a feature in severe erythroblastosisfetalis, with a disturbed blood protein level was the causative mechanism of the edema, and that the serum albumin restored the level. Studies are now in progress further to elucidate these factors. Two cases of erythroblastosis fetalis complicated by severe generalizededema successfully treated with concentrated human serum albumin are reported. The first was one of twins, in which the untreated sibling died. In the second case, blood studies were done and it was found that the use of the serum albumin corrected an early fall in the blood protein level with subsequent elimination of the severe generalized edema. It is postulated that liver damage, frequently a feature in severe erythroblastosisfetalis, with a disturbed blood protein level was the causative mechanism of the edema, and that the serum albumin restored the level. Studies are now in progress further to elucidate these factors.