Incidence and Familial Occurrence of the Congenital Anomalies of the Face, Hand and Foot

We made an epidemiological study of congenital anomalies of the face, hand and foot in newborns from 1973 to 1992 in Miyagi Prefecture which has a population of about two million. In these twenty years 579,766 babies were born in Miyagi Prefecture. Out of these newborns 3,416 babies with 3,759 congenital anomalies of the face, hand and foot were registered. Of all registered congenital anomalies, face anomalies were most commonly encountered, followed by hand and foot anomalies. Among face anomalies, in order of frequency, accessory ear was the most common, next cleft lip with or without cleft palate, cleft palate alone, cryptotia and microtia. The occurrence ratio per 10,000 live births was 9.6 in accessory ear, 6.7 in cleft lip, 6.1 in cleft lip with cleft palate, 4.2 in cleft palate alone, 2.9 in cryptotia, and 1.8 in microtia. In hand and foot anomalies, polydactyly was the most common and syndactyly the next. Incidence ratio of polydactyly was 5.8 in the hand and 6.4 in the foot. Polydactyly was the most frequent in the preaxial ray in the hand and in the postaxial ray in the foot. About half of cases of postaxial polydactyly the foot was associated with syndactyly between the fourth and fifth toe. In addition, we reported on variation of the incidence ratio and familial occurrence of congenital anomalies of the face, hand and foot.     

Worldwide time trends for symptoms of rhinitis and conjunctivitis: Phase III of the International Study of Asthma and Allergies in Childhood

In Phase III of the International Study of Asthma and Allergies in Childhood (ISAAC) time trends in the prevalence of rhinoconjunctivitis symptoms were analysed. Cross-sectional questionnaire surveys with identical protocols and questionnaires were completed a mean of 7 yr apart in two age groups comprising 498,083 children. In the 13- to 14-yr age group 106 centres in 56 countries participated, and in the 6- to 7-yr age group 66 centres in 37 countries participated. A slight worldwide increase in rhinoconjunctivitis prevalence was observed, but the variations were large among the centres and there was no consistent regional pattern. Prevalence increases in the older children exceeding 1% per year were recorded in 13 centres, including 3 of 9 centres in Africa, 2 of 15 in Asia-Pacific, 1 of 8 in India, 3 of 15 in Latin America, 3 of 9 in Eastern Europe and 1 of 34 in Western and Northern Europe. Decreasing rhinoconjunctivititis prevalence of similar magnitude was only seen in four centres. The changes were less pronounced in the 6- to 7-yr-old children and only in one centre did any change exceed 1% per year. The decrease in highest prevalence rates in ISAAC Phase I suggests that the prevalence has peaked in those regions. An increase was recorded in several centres, mostly in low and mid-income countries. The increases were more pronounced in the older age group, suggesting that environmental influences on the development of allergy may not be limited to early childhood.     

Sexual dimorphism of sulcal length asymmetry in the cerebrum of adult cynomolgus monkeys (Macaca fascicularis)

The present study aimed to quantitatively clarify the gross anatomical asymmetry and sexual dimorphism of the cerebral hemispheres of cynomolgus monkeys. While the fronto-occipital length of the right and left cerebral hemispheres was not different between sexes, a statistically significant rightward asymmetry was detected in the cerebral width at the perisylvian region in females, but not in males (narrower width of the left side in the females). An asymmetry quotient of the sulcal lengths revealed a rightward asymmetry in the inferior occipital sulcus and a leftward asymmetry in the central and intraparietal sulci in both sexes. However, the laterality of the lengths of other sulci was different for males and females. The arcuate sulcus was directed rightward in males but there was no rightward bias in females. Interestingly, the principle sulcus and lateral fissure were left-lateralized in the males, but right-lateralized in the females. The results suggest that lateralization patterns are regionally and sexually different in the cerebrum of cynomolgus monkeys. The present results provide a reference for quantitatively evaluating the normality of the cerebral cortical morphology in cynomolgus monkeys.     

Multifocal hydatid disease in a child

One of the most serious helminth infections in humans with widespread occurrence is hydatid disease. Although the majority of the cases are referred in adults, many of them have to do with children. The hydatid cysts can occur in any organ of the human body and in rare cases in a combination of different sites. We present the case of a young boy with hydatid cysts in both lungs and in the upper pole of the left kidney. The rarity of this case is the unusual combination of the cyst development in these organs without the involvement of the liver.     

PREVALENCE AND TEN-YEAR (1970-1979) INCIDENCE OF INSULIN-DEPENDENT DIABETES MELLITUS IN CHILDREN AND ADOLESCENTS IN FINLAND

ABSTRACT. The prevalence and incidence of insulin-dependent diabetes mellitus in Finnish children and adolescents were studied by means of a national register of drug-treated diabetics and hospital records. At the end of 1979 the prevalence of diabetes in children aged 0-14 was 191/100000, and in those aged 0-19, 262/100000 respectively. During the 10-year period from 1970 to 1979, 3916 new diabetics aged 0-19 years were registered. The annual incidence of diabetes was 27.3/100000 in the age group 0-19 years and 28.6/100000 in those 0-14 years. The peak incidence of diabetes in girls occurred at 12 years of age and in boys at 14 years. There was a seasonal variation in the symptom debut, with peaks in April and in September and low rates in the summer. A regional variation in the prevalence and incidence rates was evident the rates being highest in eastern and lowest in northern Finland. The prevalence of diabetes mellitus increased clearly during the observation period, and the incidence tended to increase especially during the last years. Both prevalence and incidence rates of diabetes mellitus in Finnish children are high by international standards, possibly the highest in the world.     

Trace Element Profiles in Individual Blood Cells from Patients with Down's Syndrome

ABSTRACT. The concentrations of trace elements in three different types of blood cells–erythrocytes, thrombocytes and neutrophils–were determined by nuclear microprobe analysis in 11 children with Down's syndrome (DS) and compared with those in 13 controls. The median concentration of copper in all three types of blood cells and that of calcium in erythrocytes were significantly higher in DS children than in controls. In contrast, the median levels of zinc in erythrocytes, of manganese and iron in erythrocytes and neutrophils, and of magnesium in erythrocytes and thrombocytes were significantly lower in DS than in control children. In 10 of the 11 DS children, detectable erythrocyte levels of titanium were found, which is remarkable, since this was not observed in any of the cells from the control children.     

发育期慢性铅暴露对大鼠血浆、脑脊液和海马中瘦素表达的影响

目的 研究发育期铅暴露对大鼠血浆、脑脊液和海马中瘦素表达的影响,探索瘦素是否和铅暴露引起的认知损伤机制有关。方法 通过在大鼠饮水中添加醋酸铅建造慢性铅暴露后大鼠认知损伤模型,根据饮水中醋酸铅的浓度可分为对照组 （0 ppm）、低铅组 （50ppm）、中铅组 （200ppm） 和高铅组 （1000ppm）,每组16只。采用原子吸收光谱法检测各组大鼠血浆、脑脊液和海马中铅含量;ELISA法检测大鼠血浆和脑脊液中的瘦素水平;免疫组化法观察瘦素在海马组织中的分布;Western blot法对大鼠海马中瘦素蛋白水平进行相对定量分析。结果 与对照组相比,铅暴露组大鼠血浆、脑脊液和海马中铅含量均升高,而血浆和脑脊液中瘦素水平均下降 （P < 0.05）。免疫组化结果显示,瘦素主要分布于海马CA区锥体神经细胞胞浆中。Western blot结果显示,与对照组相比,3个铅暴露组大鼠海马中瘦素蛋白表达水平略升高,但差异均无统计学意义 （P > 0.05）。结论 铅暴露可使大鼠血浆和脑脊液瘦素水平降低,这可能与铅暴露引起大鼠认知能力损伤的机制有关。     

Sonic hedgehog signaling coordinates the proliferation and differentiation of neural stem/progenitor cells by regulating cell cycle kinetics during development of the neocortex

Sonic hedgehog (Shh) acts as a morphogen in normal development of various vertebrate tissues and organs. Shh signaling is essential for patterning and cell-fate specification, particularly in the central nervous system. Shh signaling plays different roles depending on its concentration, area, and timing of exposure. During the development of the neocortex, a low level of Shh is expressed in the neural stem/progenitor cells as well as in mature neurons in the dorsal telencephalon. Shh signaling in neocortex development has been shown to regulate cell cycle kinetics of radial glial cells and intermediate progenitor cells, thereby maintaining the proliferation, survival and differentiation of neurons in the neocortex. During the development of the telencephalon, endogenous Shh signaling is involved in the transition of slow-cycling neural stem cells to fast-cycling neural progenitor cells. It seems that high-level Shh signaling in the ventral telencephalon is essential for ventral specification, while low-level Shh signaling in the dorsal telencephalon plays important roles in the fine-tuning of cell cycle kinetics. The Shh levels and multiple functions of Shh signaling are important for proper corticogenesis in the developing brain. The present paper discusses the roles of Shh signaling in the proliferation and differentiation of neural stem/progenitor cells.     

新生儿肺出血支气管肺泡灌洗液SP-A及TNF-α的变化及其相关性研究(英文)

目的近年研究发现急性肺损伤(ALI)是致新生儿肺出血的重要原因。大量研究表明肺表面活性蛋白A(SPA)和肿瘤坏死因子-α(TNFα)参与了ALI的损伤过程,但有关两者在肺出血新生儿支气管肺泡灌洗液(BALF)中的变化及关系鲜有报道。该研究旨在探讨SPA和TNFα在新生儿肺出血发生中的作用,两者间的关系及对预后的影响。方法采用斑点免疫印迹法和酶联免疫吸附法分别测定对照组(n=15),肺出血存活组急性期(n=14)、恢复期(n=14)和肺出血死亡组(n=6)新生儿BALF中SPA,TNFα和血清TNFα水平。结果存活组和死亡组新生儿肺出血急性期BALF中SPA含量(38.50±7.62,29.43±6.57)较对照组(44.88±7.48)显著降低(P=0.024,P=0),且死亡组SPA明显低于存活组急性期(P=0.015),存活组肺出血恢复期SPA水平(45.16±7.25)明显升高,接近对照组(P>0.05);而肺出血存活组和死亡组BALF中TNFα含量(208.54±64.69ng/L,319.16±46.79ng/L)较对照组(96.40±37.82ng/L)显著增加(P=0.011,P=0),死亡组比存活组急性期增加更明显(P=0),且BALF中TNFα的变化较血清中更明显,存活组恢复期BALF中TNFα水平(112.06±35.22ng/L)明显下降,接近对照组(P>0.05);肺出血患儿BALF中SPA水平的下降与TNFα的增高呈负相关(r=0.635,P=0.003)。结论SPA和TNFα参与了新生儿肺出血的肺损伤过程,为从SPA及细胞因子角度进一步认识新生儿肺出血的发病机制提供了实验依据,为新生儿肺出血的早期防治及预后判断提供了一种新的方法。     

The development of arithmetical abilities

BACKGROUND: Arithmetical skills are essential to the effective exercise of citizenship in a numerate society. How these skills are acquired, or fail to be acquired, is of great importance not only to individual children but to the organisation of formal education and its role in society. METHOD: The evidence on the normal and abnormal developmental progression of arithmetical abilities is reviewed; in particular, evidence for arithmetical ability arising from innate specific cognitive skills (innate numerosity) vs. general cognitive abilities (the Piagetian view) is compared. RESULTS: These include evidence from infancy research, neuropsychological studies of developmental dyscalculia, neuroimaging and genetics. The development of arithmetical abilities can be described in terms of the idea of numerosity -- the number of objects in a set. Early arithmetic is usually thought of as the effects on numerosity of operations on sets such as set union. The child's concept of numerosity appears to be innate, as infants, even in the first week of life, seem to discriminate visual arrays on the basis of numerosity. Development can be seen in terms of an increasingly sophisticated understanding of numerosity and its implications, and in increasing skill in manipulating numerosities. The impairment in the capacity to learn arithmetic -- dyscalculia -- can be interpreted in many cases as a deficit in the concept in the child's concept of numerosity. The neuroanatomical bases of arithmetical development and other outstanding issues are discussed. CONCLUSIONS: The evidence broadly supports the idea of an innate specific capacity for acquiring arithmetical skills, but the effects of the content of learning, and the timing of learning in the course of development, requires further investigation.     

Concentrations of dioxins and other organochlorines (PCBs,DDTs, HCHs) in human milk from Seveso,Milan and a Lombardian rural area in Italy: a study performed 25 years after the heavy dioxin exposure in Seveso

AIM: To investigate whether those who were exposed to high levels of the dioxin TCDD 25 years ago in Seveso, northern Italy still have higher than the expected levels of dioxins in their fat stores, and to investigate the concentrations of dioxins in the breast milk of mothers in Seveso and in two other regions in Italy. The load of vertically transmitted dioxins to the next generation, if being breastfed, was also investigated. METHODS: As there may be a synergistic effect of mixtures of organic chlorines, the concentrations of pesticides such as DDTs and PCBs have also been studied in the same human milk samples. Breast milk from 12 mothers from Seveso, Central Milan and a Lombardian village was collected for analysis during the first week and 1 and 3 mo after delivery. Individual samples were used for the analysis of pesticides and PCBs, whereas dioxins were analysed in pooled samples from all 12 mothers on each occasion. RESULTS: In human milk from Seveso, the TCDD concentration in fat calculated on a fresh weight basis was more than twice as high as the level in the other two regions, whereas the concentrations of investigated other toxins were lower in Seveso possible due to induction of the enzyme cytochrome P4501A, which means that the total level of dioxins was the same in all three locations. The congener profile, measured as mean toxic equivalency (TEQ) values, was the same in the Italian samples as previously reported from Stockholm. The calculations are based on the most recent WHO TCDD equivalency factors (TEF). The DDE concentration was higher in the samples from Milan than in the samples from the other two Italian regions, which may be due to the fact that, to a greater extent than in the other regions, Milanese food is imported from countries where DDT is still used as a pesticide. CONCLUSION: Twenty-five years after the dioxin catastrophe, human milk from mothers in Seveso has concentrations of the highly toxic dioxin congener TCDD that are more than twice as high as those in central Milan and a Lombardian village. This means that breastfed infants in Seveso still store an appreciable amount of TCDD in their body fat. The health consequences of this fact remain to be elucidated. The effect of the high load of DDTs in central Milan also has to be considered     

GLYCOSIDASES IN SKIN AND PLASMA IN HUNTER'S SYNDROME Abnormality of a β-galactosidase in Skin

Two patients with Hunter's syndrome (mucopolysaccharidosis type II) were studied. The exact diagnosis could be settled by the finding of clinical symptoms and signs, typical for this form of mucopolysaccharidosis, and of a greatly increased excretion of glycosaminoglycans (acid mucopolysaccharides) in the urine, as well as by the fact that the patients were half-brothers with unrelated fathers. Analyses of glycosidases in skin demonstrated the existence of low activity of β-galactosidase in both patients. β-acetylglucosaminidase was more active in both patients and β-glucuronidase in one of them than in the controls. In plasma increased activities were noted for β-glucuronidase and β-acetylglucosaminidase in both patients and of β-galactosidase and α-mannosidase activities in one of them and of α-fucosidase activity in the other. The results are very similar to those described in patients with Hurler's syndrome (mucopolysaccharidosis type I).     

Histomorphology of renal dysplasia--an autopsy study

A retrospective analysis of pediatric autopsies in the past 18 years was done with the aim of studying the histomorphology of renal dysplasia. Renal dysplasia comprised 150 (3.66%) of the 4,099 pediatric autopsies from 20 weeks of gestation to 1 year of life. Primitive ducts with the fibromuscular collar, the sine qua non of renal dysplasia, was seen in all cases. Lobar disorganization and cysts were seen in all cases except for the 7 cases of hypodysplasia. Other elements were seen in varying proportions: cartilage in 33.7%, bone in 1.08%, thickening of basement membrane of the primitive ducts in 64.13%, extramedullary hematopoiesis in 98.9%, nerve twigs in 72.8%, and nodular renal blastema in 2.17% cases. In unilateral multicystic dysplasia/renal agenesis, the contralateral kidney showed abnormalities in 44.45% and 47.37% of cases, respectively.     

Fetal jaw movement affects development of articular disk in the temporomandibular joint

Previous studies suggest that jaw movement is an important factor in the development of cartilage in the temporomandibular joint during the prenatal and postnatal periods. In the present study, the effects of fetal jaw movement on the articular disk were studied in mice by restraining the opening movement of the mouth using the mouse exo utero development system. At embryonic day 18.5, the articular disk was reduced in size in the embryos whose maxilla and mandible were sutured (sutured group) and there were changes in the cellular morphology of the mesenchymal cells in the disk. The volume of the articular disk, the total number of cells and the number of 5-bromo-2'-deoxyuridine-positive cells in the articular disk were significantly lower in the sutured group than in the non-sutured control group. Our data revealed that fetal jaw movement affects the development of the articular disk in the temporomandibular joint.     

Local and global processing of music in high-functioning persons with autism: beyond central coherence?

A multi-modal abnormality in the integration of parts and whole has been proposed to account for a bias toward local stimuli in individuals with autism (Frith, 1989; Mottron & Belleville, 1993). In the current experiment, we examined the utility of hierarchical models in characterising musical information processing in autistic individuals. Participants were 13 high-functioning individuals with autism and 13 individuals of normal intelligence matched on chronological age, nonverbal IQ, and laterality, and without musical experience. The task consisted of same-different judgements of pairs of melodies. Differential local and global processing was assessed by manipulating the level, local or global, at which modifications occurred. No deficit was found in the two measures of global processing. In contrast, the clinical group performed better than the comparison group in the detection of change in nontransposed, contour-preserved melodies that tap local processing. These findings confirm the existence of a "local bias" in music perception in individuals with autism, but challenge the notion that it is accounted for by a deficit in global music processing. The present study suggests that enhanced processing of elementary physical properties of incoming stimuli, as found previously in the visual modality, may also exist in the auditory modality.     

Early child health in Lahore, Pakistan: XII. Milestones

Psychomotor development was assessed in 1476 infants from four different levels of urbanization in and around Lahore, Pakistan. Development was assessed monthly at birth to 24 months of age by using a set of 10 milestones selected from the Denver Developmental Screening Test and the Developmental Screening Inventory. The psychomotor development of children in the upper middle (Um) class was consistent with reference population groups in Europe and North America, hence this group was used as control. There was significant delay in the psychomotor development of infants belonging to the poorer areas compared to the Um class. There was no sex difference in the development of the milestones in any study area, except for girls in the Um class who were earlier for about one month than boys in talking. Infants in the poorer areas were, on average about 3 months, delayed in their walking and fine motor activity (building a tower of 3 cubes) in comparison with the Um class. Observed disturbance in psychomotor development at an early age may affect the abilities and achievements in later life.     

Prevalence, severity and medical management of asthma in European school children in 1985 and 1991

This present study, conducted in 1991, examined trends in the prevalence, severity and medical management of asthma in European school children by repeating the protocol of a study performed in 1985, using the same schools and questionnaire. One thousand, nine hundred and one children in 1991 were compared with 1084 children in 1985. The prevalence of respiratory symptoms increased significantly by approximately one-third, although the increase in the diagnostic label ‘asthma’ did not increase significantly. Asthma severity indices (< 12 asthma attacks in the last 12 months and symptoms in the last month) were not significantly increased, except for night cough in the last month (1985 7.0%, 1991 9.9%, P= 0.008). In 1991, children with wheeze in the last 12 months were more likely to be diagnosed as having asthma and treated with bronchodilators and prophylactic drugs than in 1985. We conclude that the prevalence of asthma symptoms has increased from 1985 to 1991, but the two indices of severity of asthma are mostly unchanged. Diagnosis of asthma in children with symptoms has improved but asthma still appears underrecognized. Drug treatment of asthma has increased.     

FIBRINOLYSIS IN NEWBORNS

The fibrinolytic system was studied in 207 normal fullterm newborns during the first 5 days of life. A high, but rapidly decreasing plasminogen activator activity was found during the first 4 hours in umbilical vein blood in all of the children studied. The activity in the cord blood was lower and cannot be regarded as representative of the child. Fibrinolytic split products were demonstrated in large and rapidly decreasing amounts in serum samples without the addition of EACA but in at most small amounts in serum when EACA was added at sampling. These findings confirm the high plasminogen activator activity at birth which rapidly falls and furthermore show that there are no significant amounts of split products in vivo in the newborn. The plasminogen level was decreased in accordance with previous investigations. The high activator activity is counterbalanced by adequate inhibitory protection with an increase of the α₂-macroglobulin and inhibitors of plasminogen activation and the adult content of antiplasmin. The mean fibrinogen values in the first 48 hours of life are in the lower part of the normal range, but increase on the third day to a significantly higher level.     

Hydrocephalus manifestation in the genetic polydactyly/ arhinencephaly mouse (Pdn/Pdn)

ABSTRACT  The genetic polydactyly/ariiinencephaly mouse, Pdn/Pdn , exhibits severe polydactyly both in the fore-and hindlimbs, hydrocephalus, and agenesis of the olfactory bulbs, corpus callosum, and anterior commissure. The mechanism of hydrocephalus manifestation in Pdn/Pdn was investigated in the present study. Ink was injected into the left lateral ventricle in the Pdn/Pdn and +/+ newborn mice. After incubation at 32°C for different time intervals, the heads were fixed in Bouin's solution and were subsequently decalcified in 0.5 mol/L of EDTA solution, paraffin sectioned, and stained with hematoxylin and eosin.
Ink spread into the 3rd and right lateral ventricles and flowed to the 4th ventricle and Magendie's foramen rapidly in Pdn/Pdn mice. This rapid spread was due to the dilatation of the interventricular foramen and that the lateral ventricle was directly connected with enlarged 3rd ventricle in Pdn/Pdn. In spite of the rapid spread of ink in the cerebrospinal fluid pathway, ink was not observed in the subarachnoid space around the superior sagittal sinus at 3.5 or 10 hours in Pdn/Pdn mice.
The superior sagittal sinus was narrower in Pdn/Pdn than in +/+, and the arachnoid villi were not observed in Pdn/Pdn. From these observations, we suggested that absorption of cerebrospinal fluid from the arachnoid villi in the superior sagittal sinus stagnated and that stagnation of the fluid in the ventricles was the cause of hydrocephalus in Pdn/Pdn mice.     

Maldescent of the Thymus: 34 Necropsy and 10 Surgical Cases, Including 7 Thymuses Medial to the Mandible

Among 3236 pediatric necropsies over 23 years, abnormal position of thymic tissue was recorded in 34 cases. Cardiac anomalies, predominantly those seen in DiGeorge syndrome, were present in 24; 3 had noncardiac anomalies only, 4 had other diseases, and 3 were sudden infant deaths. Mediastinal thymic tissue was absent in 22 cases, small or unilateral in 7, and normal in 5. The maldescended thymic tissue was unilateral in 18, bilateral in 11, and multiple on one or both sides in 5. It was situated near the thyroid gland in 19, lower in the neck in 6, and higher in 9, including 7 medial to the submandibular salivary gland and 1 at the base of the skull. The maldescended tissue approached the size of a normal lobe of thymus in eight and was 2.4 to 0.1 cm in the remainder. Over the same period, in only two cases was no thymic tissue found. Among 68,000 surgical specimens over 40 years, there were 10 cases of ectopic thymus in the neck, including 1 cutaneous and 4 cystic. This frequency of thymic tissue in the neck may explain why lymphoid tissues are sometimes relatively normal in cases of absent mediastinal thymus and behooves a search in the submandibular salivary gland region and higher before diagnosing thymic agenesis.