[Are our babies becoming larger?].
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Adult↗
Biomedical subjects
A Ornoy
Publications and source records attributed to A Ornoy.
Inattention, hyperactivity and speech delay at 2-4 years of age as a predictor for ADD-ADHD syndrome.
In the Jerusalem Institute for Child Development children with various developmental disorders at ages of 0-5 years are examined. Thirty-six children aged 2-4 years were examined by us and were found to have inattention, hyperactivity and speech delay with an IQ or DQ above 70 and were reexamined at 7-14 years of age. They were compared to a group of 27 control children. All children had a complete neurodevelopmental examination using the Touwen & Prechtel examination for Minor Neurological Dysfunction. They also had a Pollack tapper test for the identification of learning disabilities and the Conners parent's and teacher's hyperactivity rating scales. Of the 36 children from the research group 20 studied in special education classes because of behavioral disorders, inattention, and severe learning disabilities. They all had ADD-ADHD. There were 16 children in regular schools, of whom 9 had ADD-ADHD. In the control group only one child had ADD-ADHD. A very high number of the research group children failed in 2 or all 3 tests used in this study in comparison to controls. It seems that "soft" neurological signs with hyperactivity, inattention and speech delay may be early clinical signs of ADD-ADHD as 80% of the children with these clinical features developed ADD-ADHD during early school age.
Attention↗
Clinical teratology.
The field of teratology has become increasingly important in preventive medicine programs. By avoiding specific teratogenic agents, many birth defects can be prevented. In this review we will summarize the currently documented teratogenic agents in humans.
Abnormalities, Drug-Induced↗
Enhancement of osteoinduction by vitamin D metabolites in rachitic host rats.
Diaphyseal bone from normal Sprague-Dawley rats was delipidated in chloroform-methanol and demineralized in 0.6 N HCl at 4 degrees C. The bones were then implanted for 7-28 days into rats made rachitic by a low-phosphate, vitamin D-deficient diet (VDP-) for 3 weeks. Bones from VDP- and normal rats were also implanted into normal hosts. When normal rats were used as the host environment, a consistent sequence of cartilage induction and bone formation was observed. Demineralized rachitic bone (RB) implanted into normal host rats resulted in cartilage and bone induction similar to that seen for normal bone (NB) implants. Transmission electron microscopy of RB in normal hosts revealed morphologically normal chondrocytes and cartilage matrix with normal mineralization. In contrast, implantation of NB in VDP- hosts resulted in delayed chondrogenesis and lack of calcification. Furthermore, similar results were observed when RB was implanted into VDP- hosts. Treatment of VDP- hosts with either 1 alpha-hydroxyvitamin D3 or 24,25-dihydroxyvitamin D3 did not accelerate the sequential appearance of precartilage or cartilage. However, 24,25-(OH)2D3 administered alone or in combination with 1 alpha-OHD3 significantly increased the amount of calcified cartilage observed at 2 weeks postimplantation compared to implants from either untreated VDP-hosts or those treated only with 1 alpha-OHD3. New bone formation was observed at 4 weeks postimplantation in all vitamin D-treated groups as determined by von Kossa staining or direct electron microscope examination. There was no apparent difference in the quantitative or qualitative bone formed within the various vitamin D-treated groups. Serum calcium and phosphorus levels were lower and alkaline phosphatase levels were higher in VDP- hosts compared with normal animals or those treated with vitamin D metabolites. The results of this study show a reduction in the capacity of progenitor cells in VDP- rat hosts to respond to osteoinductive factor(s). This impaired response appears to be corrected by vitamin D metabolites.
24,25-Dihydroxyvitamin D 3↗
Prevalence of disabilities in a national sample of 7-year-old Israeli children.
The prevalence of chronic conditions and illnesses causing disability in Israeli Jewish children aged 7 years born in 1975 was studied on the basis of a national sample (n = 7,739). Eighty medical conditions causing disability were defined. The study showed a total disability rate of 17.5%, which is higher than that reported on a similar national sample of 3 year olds (prevalence of 6.9%). The percentage of disabilities among very low birthweight children and those with family problems was four times greater than in the total population. Mild retardation and undefined learning problems were more prevalent among children of mothers with low educational level and among children whose birth order was fourth or more. Asthma and spastic bronchitis were more prevalent among children whose mothers were of European/American origin (P less than 0.05). Behavior and mental disorders, learning problems, speech and language disorders were more prevalent among male children. Two-thirds of the children with a diagnosed problem also had at least one functional disability. There were relatively more children from lower social classes in the special education schools than in the national sample. Increased prevalence of disabilities among children of very low birthweight, low maternal educational level, high birth order, and those from families whose origin is Asian/African and from families with intrafamilial problems defines the children at risk for disabilities and placement in special education schools.
Birth Order↗
Effects of 1 alpha(OH)-vitamin D3 and 24,25(OH)2-vitamin D3 on long bones of glucocorticoid-treated rats.
Glucocorticoids may induce osteopenia in experimental animals and in man. In order to study the possible effects of vitamin D metabolites in the prevention of glucocorticoid-induced osteopenia in rats, we administered 1 alpha(OH)-vitamin D3, 24,25(OH)2-vitamin D3 or a combination of both metabolites, by intragastric intubation, to rats treated daily by intramuscular injections of 10 mg/kg cortisone acetate. Treatment with the vitamin D metabolites started after 1 month of glucocorticoid therapy, at the time osteopenia was already present. Cortisone acetate decreased the gain weight, increased alkaline phosphatase (AP) and decreased Ca serum levels. It also decreased tibial wet and ash weight and tibial Ca content. Computerized histomorphometry of sections from the upper tibia showed decreased epiphyseal bone volume and increased bone marrow volume; decreased height of hypertrophic cartilage in the growth plate and decreased amount of persisting cartilage in the metaphyseal bone trabeculae were also observed. Administration of 24,25(OH)2D3 alone did not reduce these glucocorticoid-induced bone changes and sometimes even worsened them. 1 alpha(OH)D3 reversed many of the deleterious effects of cortisone acetate. It reduced serum AP levels, increased serum Ca levels, increased bone ash weight, epiphyseal and metaphyseal bone volume, with a concomitant reduction in epiphyseal and metaphyseal bone marrow volume. The best results were obtained by a combination of 1 alpha(OH)D3 and 24,25(OH)2D3. It is presumed that both metabolites are needed to reduce the impact of glucocorticoids on bone. 1 alpha(OH)2D3 acts on the gut, increasing Ca absorption (which was decreased by glucocorticoids), and 24,25(OH)2D3 directly acts on bone to enhance bone formation and mineralization.
24,25-Dihydroxyvitamin D 3↗
[Teratological counseling in Israel].
For the past 6 years this laboratory has offered counseling on external factors which may harm the fetus. The number of calls on the service doubles yearly. From 1987 through the first half of 1990 there were 1182 calls, about half from women and half from physicians, nurses, geneticists, etc., most during the first trimester. In 88% there was no increased risk for congenital malformations as a result of the exposure, or the increased risk was minimal. In only 6% of cases was there significant increased risk, well above the 3% found in pregnancies in general. In 6% we were not able to assess accurately fetal risk, although we could assume it was relatively small. Outcome of pregnancy was available in 27% of the cases. There was no increase in spontaneous abortions, prematurity, or congenital anomalies in pregnancies in which we had decided there was no increased risk for malformations. However, the number of cases is still too small for significant conclusions. Reliable information concerning factors which may influence the fetus is important in allaying fear and anxiety in families in which fetal risk is not increased. In cases in which fetal insult is suspected, appropriate means of prenatal diagnosis are suggested, and the option of terminating pregnancy is offered.
Abnormalities, Drug-Induced↗
Recurrent tetraamelia and pulmonary hypoplasia with multiple malformations in sibs.
A term amelic female infant was born to an apparently nonconsanguineous Arab Moslem couple. This was followed by the birth of 4 normal children. Afterwards, in 2 subsequent pregnancies, 2 amelic fetuses were diagnosed by transabdominal ultrasonography in the 18th and 12th week of gestation. Pregnancies were terminated and on autopsy both amelic fetuses had severe lung hypoplasia and aplasia of the peripheral pulmonary vessels. The first fetus also had apparently low-set ears and micrognathia, whereas the last had hydrocephaly and left cleft lip beside the lung hypoplasia and aberrant pulmonary artery. This appears to be a new autosomal recessive malformation syndrome.
Abnormalities, Multiple↗
Acrania: anencephaly resulting from secondary degeneration of a closed neural tube: two cases in the same family.
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Adult↗
Ultrastructure and function of the rat yolk sac: damage caused by teratogenic anti-VYS serum and recovery.
It was hypothesized that heterologous anti-rat visceral yolk sac serum (AVYS) exerts its teratogenic effect by reducing the endocytosis of serum proteins by the visceral yolk sac (VYS), thus reducing the supply of amino acids to the embryo and VYS. To evaluate this hypothesis, we studied the effect of teratogenic AVYS on the endocytic function of the VYS and the ultrastructure of the VYS and parietal yolk sac (PYS). Rat conceptuses were exposed to a teratogenic dose of AVYS on the 10th day of gestation in vivo or in vitro. Control and AVYS-exposed specimens were collected 24-192 hr later and prepared for scanning and transmission electron microscopy (SEM and TEM, respectively) utilizing standard procedures. The Endocytic Index was calculated for the VYS utilizing standard procedures. Approximately 97% of the in vivo exposed and 94% of the in vitro exposed embryos were morphologically abnormal. Ultrastructural observations showed that exposure to AVYS in vivo or in vitro caused severe damage to the VYS endodermal epithelial cells with loss of cellular borders, reduction in the number and length of microvilli, and increased cellular inclusions; and some damage to PYS endodermal cells with increased blebbling and decreased cell number. Recovery was evident at 72 hr and complete by 96 hr. The Endocytic Index was significantly reduced in the VYS 24 and 48 hr after injecting AVYS into the pregnant rat but was not significantly different at 96 and 192 hr. Our results show that the AVYS antiserum damaged visceral endodermal epithelium experienced ultrastructural recovery with parallel functional recovery. These studies suggest that transient yolk sac placental ultrastructural damage and dysfunction was probably sufficient to cause irreversible damage to the developing embryo during early organogenesis. We conclude that the proximate effect of the AVYS was on the plasma membrane of the visceral endoderm and that decreased pinocytosis is a consequence of this effect.
Animals↗
Direct and sex-specific enhancement of bone formation and calcification by sex steroids in fetal mice long bone in vitro (biochemical and morphometric study.
The study was carried out to examine the direct effect of the sex hormones 17 beta-estradiol (E2) and testosterone on the modeling of cultured fetal mouse long bones separated according to their sex. The culture system used allowed for the simultaneous assessment of bone growth, mineralization, and resorption on each bone. Bones from 16-day-old male and female mouse fetuses were cultured in BGJ medium, supplemented with either 10% fetal calf serum or 4 mg/ml BSA (serum-free medium) for 48 h. The bones were harvested, and their length; the length of their diaphyses; their hydroxyproline, calcium, and phosphorus contents; and their 45Ca release were measured. Histomorphometric analyses on midlongitudinal sections of bones from parallel experiments were also performed. The results indicate that in medium supplemented with 10% fetal calf serum, E2 had a dose-dependent stimulatory effect on bone formation and mineralization at 10(-7) and 10(-9) M, with no effect on bone resorption. This effect was specific to bones from female mice and to E2, since 17-alpha-estradiol had no effect. Testosterone had similar effects specific to bones from male mice, resulting in the stimulation of bone formation and mineralization at 10(-7)- and 10(-9)-M concentrations. These effects were absent when serum-free medium was used. E2 and testosterone had an anabolic effect on endochondral and periosteal bone formation and mineralization, but no effect on bone resorption. This effect is dependent on the presence of a serum factor(s).
Animals↗
[Family health center follow-up in preschool children].
The duration of follow-up at family health centers (FHC) was determined from a national prevalence study of chronic conditions and illnesses causing disability in preschool children. The sample comprised 8,702 children (12% of the 71,372 in the national Jewish birth cohort of 1980) who had reached the age of 3 years at the time of the study. The sample originated from 118 of the 870 FHC in areas of Jewish population which included FHC managed by municipalities, sick funds and the Ministry of Health. With increase in age there was a significant decrease in attendance at the FHC. Thus at 6 months of age, 97% of the sample attended the FHC, while at 3.5 years the follow-up rate had fallen to 33%. Children of mothers of Asian origin, of mothers with less than 10 years of schooling, and of mothers 19 years old or less on delivery, as well as first-born children, showed a higher rate of attendance at age 3 than the others. Higher attendance at age 3 was also registered in the south of the country, especially rural areas. More children with diagnosed medical problems attended at age 3 than healthy children. More children born with birth weights of 1,500 g or less dropped out of the FHC during their first year of life. The findings suggest that the purpose, content and efficiency of FHC be reexamined in light of changes in the needs of the target population due to educational and technological progress.
Age Factors↗
Spontaneous abortions following oral poliovirus vaccination in first trimester.
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Abortion, Spontaneous↗
Effects of pulsing electromagnetic fields on the prenatal and postnatal development in mice and rats: in vivo and in vitro studies.
Electromagnetic fields (EMF) might have various biological effects on the developing embryo. We studied the effects of pulsing electromagnetic fields (PEMF) on the in vitro development of preimplantation mouse embryos and of early somite rat embryos as well as on the in vivo development of rat embryos. We used PEMF at frequencies of 1, 20, 50, 70, and 100 Hz with a tension of 0.6 V/m. The embryos were exposed to PEMF throughout the experimental period. PEMF at frequencies of 20 and 50 Hz were embryotoxic, inhibiting over 50% of blastocysts from hatching and further development, all within 72 h of culture. PEMF at frequencies of 50 and 70 Hz induced 22% and 30% incidence of malformations in 10.5 day old rat embryos after 48 h in culture. The main malformations were absence of telencephalic, optic, and otic vesicles and of forelimb buds. In addition, retarded growth and development manifested by fewer somites, reduction in crown-rump length, and retarded closure of the neural tube were found in many embryos. No significant pathological changes were found by TEM in PEMF-exposed embryos. Disappearance of microvilli and collapse of apical parts of endodermal cells were observed by SEM in many yolk sacs of embryos exposed to 50 and 70 Hz PEMF. A slightly reduced litter average, a reduction or increase of weight, and a delay in eye opening was observed among offspring of pregnant rats exposed throughout pregnancy to PEMF at frequencies of 20, 50, and 100 Hz. No malformations were observed among these offspring. The mechanism of PEMF-induced embryotoxicity and teratogeneity is unknown, as is the mechanism of the "protective effects" of the mother on the rat embryos exposed to PEMF in vivo.
Abnormalities, Multiple↗
The biphasic effect of triiodothyronine compared to bone resorbing effect of PTH on bone modelling of mouse long bone in vitro.
To examine the effects of T3 on fetal long bone modelling the radii and ulnae of 16 day old fetal mice were grown in vitro for two days. Their growth, mineralization, and resorption were assessed by measuring diaphyseal length, calcium and phosphorus content, hydroxyproline content, and the release of incorporated 45Ca. The effects of T3 were compared to the effects of 1-34 PTH, a known resorbing agent, on the same system. Devitalized bones were used as a control. The results showed that T3 had a biphasic effect. At high concentrations (10(-5) M-10(-6) M) T3 inhibited the growth of the bones as indicated by their diaphyseal length and hydroxyproline content. Calcium and phosphorus content were significantly decreased while 45Ca release was increased. Similar effects were also found after the addition of 1-34 PTH to the media. However, T3, at lower concentrations (10(-7) M-10(-9) M), stimulated the growth and calcification of the bones as indicated by an increase in diaphyseal length and the hydroxyproline, calcium, and phosphorus content. 45Ca release was significantly decreased at these concentrations. Neither T3 nor 1-34 PTH affected devitalized bones in the same system. The results suggest that at physiological concentrations, T3 has a direct, anabolic effect on bone, which may explain its major role in the growth process of various species. At high doses, however, T3 stimulates bone resorption in a way similar to PTH.
Animals↗
Embryonic resistance to chemical and physical factors: manifestation, mechanism, role in reproduction and in adaptation to ecology.
Chemical and physical factors may adversely affect embryonic development. As an example of chemical factors, the effects of diabetic metabolic factors on embryonic development in mammals was reviewed. The existence of a stage-dependent reaction of embryos was found. At preimplantation stages diabetic metabolic factors are embryotoxic and lethal, and the blastocysts reacted by an "all-or-none" response. Early somite embryos showed a higher resistance to the effects of diabetic metabolic factors resulting in various types of malformations. Both groups of embryos showed a very high sensitivity to the effects of combined diabetic metabolic factors. Congenital defects in term foetuses were lower than those observed during middle phases of pregnancy because some of the severely malformed embryos resorb during gestation. The effects of temperature on embryonic development were presented as an example of physical influences. In man, hyperthermia in pregnancy seems to correlate with defects in the development of the nervous and skeletal systems. In domestic animals, changes in environmental temperature correlated with depressions of reproduction rate. In laboratory animals, hyperthermia caused the development of congenital malformations. Stage-dependent as well as genetic differences in embryonic susceptibility to hyperthermia were found. Critical periods in sensitivity of embryos to hyperthermic influences were also observed. It has been shown that, in spite of similar external manifestations of the reaction of embryos to effects of diabetes and hyperthermia, the mechanism of these reactions was different. High resistance of early reptile and bird embryos to influences of temperature was considered as an example of morphofunctional adaptations in early embryogenesis of vertebrates to their development in terrestrial conditions.
Animals↗
The effects of serum from women with miscarriages on the in vitro development of mouse preimplantation embryos.
It is generally believed that some human miscarriages result from embryotoxic factors existing in the sera. To study the embryotoxicity of such sera, 3.5-day-old mouse blastocysts were cultured for 72 h on 80% sera from different groups of women. After 72 h there was no blastocystic development in 53.2% of the cases grown on sera from women after two or more miscarriages, and none in 33.6% of the blastocysts grown on sera from women after one miscarriage, as compared with 8.2% and 12% respectively on control sera. Sera from women with miscarriages were divided into 'high risk' (50% or more embryotoxicity) and 'low risk' (less than 50% embryotoxicity) sera. The 'high risk' sera from two or more miscarriages caused an average of 72.1% undevelopment, while the 'low risk' sera (less than 50% embryotoxicity) from the same group caused 33.6% undevelopment. The 'high risk' sera from one miscarriage were embryotoxic to 55.8% of the blastocysts and the 'low risk' sera from the same group caused only 8.7% undevelopment. No significant differences were found in the mean serum concentrations of folic acid, zinc and copper of many of the experimental groups, in comparison with controls. The embryotoxic factor/s which exist in the 'high risk' sera from women with miscarriages are still not known.
Abortion, Spontaneous↗
[Effects of surface demineralization on fracture healing in rat tibias].
Surface demineralization of bone in vivo induces new cartilage and bone formation locally. We studied the effects of local surface demineralization of the tibia in the rat on the process of fracture healing. We found that demineralization for 20 minutes with 0.5N HCl induced in the first 10 days following fracture less cartilaginous callus, with less calcium and magnesium, as compared to controls. However, from the second week on, the amount of cartilaginous callus in HCl-treated and control fractured bones was similar. Bony callus was greater in HCl-treated bones throughout the experiment, but X-rays showed poor bone union 5-8 weeks following fracture. Surface demineralization of bone in vitro induces local cartilage and bone formation, but inhibits good fracture healing.
Animals↗