Identification of female carriers of adrenoleukodystrophy

The concentrations of very long chain fatty acids in plasma and cultured skin fibroblasts were studied in 96 women who were obligate heterozygotes for X-linked adrenoleukodystrophy, in 34 women who were mothers of single probands with ALD, and in 32 normal women of comparable age. Discriminant analysis was used to develop a classification function for the plasma values. With this function, plasma values in 88% of the women who were obligate heterozygotes for ALD and 77% of the mothers of single probands were identified as abnormal. With subsequent inclusion of the fibroblast assay data, abnormal plasma values were found in 93% of the obligate heterozygotes.     

Intelligence of children of epileptic mothers

Intellectual performance was investigated in a group of 148 children of epileptic mothers enrolled in a prospective study during pregnancy, and in 105 control children; 121 of the 148 children (82%) were examined together with the control group at the age of 5 1/2 years. The intelligence of 116 study and 104 control children was assessed by both verbal (Wechsler Preschool and Primary Scale of Intelligence) and nonverbal (Leiter International Performance Scale) methods. The prevalence of mental subnormality among the remaining 32 study children was calculated on the basis of psychologic assessments done outside our study, or school achievement, or both. Of the 148 study group children, 131 had been exposed in utero to antiepileptic drugs, most commonly phenytoin (103 exposed). The prevalence of mental deficiency in the study group (1.4%) was either the same or only slightly elevated in comparison with that in the general population. In the control group, there were no mentally deficient children. The mean intelligence quotients obtained at the 5 1/2-year examination were significantly lower in the study group than in the control group. There was no increased risk of low intelligence attributable to fetal exposure either to antiepileptic drugs below toxic levels or to brief maternal convulsions. In a few cases, there seemed to be a genetic connection between epilepsy in the mother and poor intellectual performance in the child. A high number of minor anomalies was associated with a lower mean intelligence quotient in both the study and the control groups. However, those features previously reported as typical of children of epileptic mothers, and those shown to be associated with phenytoin exposure in a previous phase of this study, did not predict low intelligence in the affected children.     

Theophylline in treatment of apnoea of prematurity

ABSTRACT. In order to determine the usefulness of theophylline in the management of apnoea of prematurity, a double blind trial was carried out by using six bottles of solution, three of which contained theophylline and the other three contained a placebo in the same base as theophylline. The incidence of apnoeic episodes diminished within 6–12 hours of commencement of therapy in 10 of 15 patients in the theophylline group with no further episodes over the next 48 hours in contrast to no response in 11 of 14 patients in the placebo group (P < 0.01). Treatment with a known solution of theophylline (following failure in the trial) resulted in termination of apnoeic spells in 8 of 11 patients in the placebo group and in 1 of 4 patients in the theophylline group. Three of the 14 patients in the placebo group and one of the 15 patients in the theophylline group have been excluded from the statistical analysis as they suffered from apnoea associated with fatal conditions     

Influence of transcutaneous oxygen monitoring on the incidence of retinopathy of prematurity

This study was performed to determine whether the use of continuous transcutaneous oxygen tension (tcPO2) monitoring could reduce the incidence of retinopathy of prematurity in preterm infants receiving oxygen therapy. A total of 296 infants with birth weights less than or equal to 1,300 g were randomly assigned to a continuous monitoring or a standard care group. Infants in the continuous monitoring group had tcPO2 monitored continuously as long as they required supplemental oxygen, and infants in the standard care group had tcPO2 monitored only during the more acute state of their illness. Management of both groups was otherwise identical. Of 148 infants in the continuous monitoring group, 101 survived; of the 148 patients in the standard care group, 113 survived. Mean birth weights and gestational ages were similar for both groups. Duration of mechanical ventilation and oxygen therapy was also similar. The overall incidence of retinopathy of prematurity was 51% in the continuous monitoring group and 59% in the standard care group. As birth weight for infants greater than or equal to 1,000 g increased, a higher risk of retinopathy of prematurity developing was noted in the standard care group. Cicatricial retinopathy of prematurity developed in four infants in the continuous monitoring group and five in the standard care group. These results suggest that continuous tcPO2 monitoring may reduce the incidence of retinopathy of prematurity in infants with birth weights greater than 1,000 g but not in the smaller infants in whom this complication occurs more frequently and is more severe.     

Disorders of interstitial cells of Cajal

Interstitial cells of Cajal (ICCs) have, in the past 2 decades, been recognised as important elements in the regulation of gastrointestinal motility. Specifically, they have been shown to be critical for the generation and propagation of electrical slow waves that regulate the phasic contractile activity of gastrointestinal smooth muscle, and for mediating neurotransmission from enteric motor neurons to smooth muscle cells. These different functional roles are carried out by different phenotypic classes of ICC that have discrete distributions within the tunica muscularis. Identifying the functional roles of ICC within the gut has been facilitated by studying mutant mice deficient in ICC, either as a consequence of loss of the tyrosine kinase receptor, Kit, or its ligand, stem cell factor, both of which are necessary for normal ICC development. In humans, under certain pathophysiological conditions, loss or defects in ICC networks appear to play a role in the generation of certain motility disorders. Alterations in ICC distribution have been reported in conditions such as achalasia, chronic intestinal pseudoobstruction, Hirschsprung disease, inflammatory bowel diseases, and slow transit constipation. Molecular and genetic techniques are helping researchers to determine whether defects in ICC networks are the cause of motility disorders, or whether the disrupted ICC networks are a consequence of gut dysfunction.     

Two cases of female hydrocele of the canal of nuck

The processus vaginalis within the inguinal canal forms the canal of Nuck, which is a homolog of the processus vaginalis in women. Incomplete obliteration of the processus vaginalis causes indirect inguinal hernia or hydrocele of the canal of Nuck, a very rare condition in women. Here, we report 2 cases of hydrocele of the canal of Nuck that were diagnosed with ultrasonography in both cases and magnetic resonance imaging in 1 case to confirm the sonographic diagnosis. High ligation and hydrocelectomy were conducted in both patients. In 1 patient, 14 months later, the occurrence of contralateral inguinal hernia was suspected, but did not require surgery. The other patient had a history of surgery for left inguinal hernia 11 months before the occurrence of right hydrocele of the canal of Nuck. In both cases, the occurrence of an inguinal hernia on the contralateral side was noted.     

Contribution of MRI to the diagnosis of cerebral lesions of adrenoleukodystrophy

33 cases of adrenoleukodystrophy in children have been studied. Brain MRI was performed in these patients in order to appreciate the benefits of this technic in patients presenting with the cerebral type of ALD [21]. 12 neurologically asymptomatic patients with the same biochemical disorder were studied. In both groups, MRI is the best imaging modality. In symptomatic patients lesions were clearly demonstrated with excellent clinical correlations. In addition, MRI can depict brain lesions in asymptomatic patients before devastating brain damage occurs. MRI is the essential step before proposing specific treatment to these patients.Presented at the ESPR meeting in Munich 1990. Selected for publication by an International Group of the ESPR     

Influence of an antagonist of slow-reacting substance of anaphylaxis on the cardiovascular manifestations of hypoxia in piglets

Leukotrienes have been implicated in the pathogenesis of hypoxic pulmonary hypertension in adult animals and in persistent pulmonary hypertension with accompanying hypoxemia in the neonate. In order to elucidate the role of leukotrienes in hypoxic pulmonary hypertension in a young animal model, the effects of a leukotriene antagonist, FPL 57231, were evaluated in anesthetized piglets. Cardiac output and vascular pressures were measured and pulmonary and systemic vascular resistances calculated prior to and during hypoxia. These measurements were compared during continued hypoxia between a control and treatment group which received FPL 57231. FPL 57231 infusion resulted in significant decreases in mean pulmonary artery pressure (p less than 0.04), pulmonary vascular resistance (p less than 0.01) and the ratio of pulmonary/systemic vascular resistance (p less than 0.01). Systemic vascular resistance fell approximately 25% from hypoxic baseline (p less than 0.01) while PVR decreased 54%. There were no differences between groups in mean systemic arterial pressure, cardiac output, pH, or PaCO2. In addition, pretreatment with FPL 57231 attenuated the hemodynamic response to hypoxia. These data suggest that leukotrienes may, in part, mediate hypoxic pulmonary vasoconstriction in piglets.     

Assessment of the effectiveness of Androcur in the treatment of precocious puberty

The data are provided on the continuous use of Androcur in the treatment of genuine precocious puberty in children. The drug produced a beneficial effect in 100% of cases in respect to suppression of the secondary sexual characters, menstrual function in girls, and behavior normalization in boys. During treatment, the improvement of the growth prognosis was negligible. Stabilization of the processes of osseous maturation requires administration of the maximal drug doses, which may suppress glucocorticoid function of the adrenals. This fact should be taken into account during treatment, particularly on its discontinuation. The treatment should be discontinued according to the schedule similar to that applied in glucocorticoid discontinuation.     

Estimation of the age of bruising

Paediatricians are often requested to give an opinion on the age of a non-accidental bruise. In forensic textbooks, the colour changes which a bruise undergoes with time are not based on research in children. The purpose of this study was to document the sequence of colour changes in photographs taken following accidental bruising in children. Fifty accidental bruises of known age in 23 children were photographed by a medical photographer using the same equipment throughout. The photographs were reviewed by a single observer, blind to the true age of the injury, who described the colours present in the bruise. Red colouration was seen in 15 out of 37 bruises which were less than one week old. Yellow colouration was seen in 10 out of 42 bruises over one day old. Aging of bruises from photographs was much less precise than textbooks imply.     

甲基泼尼松龙治疗川崎病的疗效及对冠状动脉影响的探讨

目的探讨甲基泼尼松龙治疗川崎病的疗效。方法75例川崎病患儿,随机分为3组A组(33例)用静脉免疫球蛋白(IVIG)治疗,B组(22例)用甲基泼尼松龙治疗,C组(20例)联用IVIG 甲基泼尼松龙治疗。观察3组患儿用药后体温、WBC、血沉(ESR)、C反应蛋白(CRP)的变化,并动态观察左、右冠状动脉内径变化。结果①用药后,B、C组患儿在体温降至正常所需天数、ESR、CRP变化方面均少于A组,而B组同C组比较差异无显著性。②在急性期、治疗后1个月及6个月,左、右冠状动脉内径3组比较差异无显著性。③治疗后1个月,A、B和C组分别有3例、1例和2例患儿产生新的冠状动脉扩张,有6例、3例和3例患儿冠状动脉内径有缩小但仍然扩张,有17例、7例和8例扩张的冠状动脉恢复正常。3组比较,差异无显著性。治疗后6个月,3组仍然有冠状动脉扩张的患儿分别为4例、1例和2例。3组比较,差异无显著性。结论甲基泼尼松龙治疗川崎病,不仅在降温、ESR和CRP的恢复方面有效,而且能够促进扩张的冠状动脉恢复,减少冠状动脉病变的发生。     

Effect of cerebral organic changes on the age of manifestation of childhood epilepsy

In the present study, the influence of organic alterations in the brain on the age of manifestation of epilepsy was investigated by means of cranial computer tomography (CCT) in 307 children and adolescents. 38% of these patients revealed abnormal morphological findings in the CCT. Whereas in children with primary generalized and partial epilepsy the vast majority (80% and 75% respectively) showed normal findings, this only applied to barely half of the patients with secondary generalized epilepsy. The pathological CCT findings were characterized mainly by diffuse alterations in primary generalized epilepsy. On the other hand, children with secondary generalized epilepsy showed above-average focal defects. The age of onset of the disease showed a close relation with the CCT findings. In patients with pathological CCT alterations, the epilepsy was manifested very much earlier than in the reference group. However, the special features of the age distribution in relation to the CCT findings only applied to secondary generalized epilepsy. Thus 80% of the diseases in the first year of life involved this form of epilepsy (in the vast majority, West syndrome), in which pathological CCT alterations were present almost without exception. These results made it evident that exogenous factors have a crucial effect on the age of manifestation, the clinical features and course of epilepsy.     

Mutations of Cxorf6 Cause a Range of Severities of Hypospadias

PurposeMutations in CXorf6, a recently-described candidate gene involved in the development of male genitalia, have been found in patients with 46, XY disorders-of-sexual-development (46, XY DSD) and severe hypospadias. To date, there has been no data regarding CXorf6 in isolated hypospadias without DSD. This study aimed to characterize the potential role of CXorf6 in such patients.Material and MethodsForty-one patients with isolated hypospadias of various severity, and 30 controls were included. DNA was extracted from excess foreskin collected during surgery. Direct sequencing for coding exons 3-6 of CXorf6 and their flanking splice sites was performed. Secondary and tertiary structures of the protein were predicted using NNpredict and PHYRE engines.ResultsFour mutations (9.7%) were identified. One missense mutation (V432A) and two deletions (del324G, predicted to cause a stop codon L121X) occurred in patients with penoscrotal and proximal hypospadias. One patient with subcoronal hypospadias had a CAG repeat amplification in the second polyglutamine domain of CXorf6. Secondary structure prediction indicated that this insertion occurred in a helix element of the protein. The tertiary structure prediction showed an alteration of the shape of the protein and crowding between domains. We also found a high incidence of polymorphisms (12.2%) in hypospadiac patients, (haplotype N589S/P286S in 4 cases).ConclusionsCXorf6 mutations occur not only in 46 XY DSD but also in isolated hypospadias of varying severity. We also describe the first CAG repeat amplification of CXorf6. However, the specific events associated with these mutations and the precise function of CXorf6 remain to be investigated.     

160例儿童急性白血病免疫表型分析

目的　免疫表型可以确定细胞的来源和分化阶段 ,是急性白血病的重要生物学特征。该文了解儿童急性白血病 (AL)抗原表达规律、分布情况并探讨其临床意义。方法　采用流式细胞术直接或间接免疫荧光法检测 1 6 0例儿童AL的免疫表型。结果　 1 6 0例AL中 ,急性淋巴细胞白血病 (ALL) 1 1 2例 ,急性髓细胞白血病(AML) 4 8例。 1 1 2例ALL中 ,T系ALL 1 2例 (1 0 .7% ) ;B系ALL(不包括成熟B ALL) 93例 (83.0 % )。ALL中 ,1 3.8%有髓系抗原表达 ,以CD33阳性最常见 ;AML中 ,4 0 %有淋系抗原表达 ,以CD7阳性率最高。儿童AML淋系抗原表达阳性率高于儿童ALL髓系抗原表达 (P <0 .0 1 )。CD1 4在儿童M 4和M 5的表达频率为 77.8%。B系ALL中CD34阳性率 5 8.5 %。AML中 ,CD34的表达频率为 5 5 .3% ,其中M1和M 2的CD34阳性率为 76 .5 % ,高于其它AML病人的CD34阳性率 (4 3.3% ) ,P <0 .0 5。HLA DR抗原在M 3的表达频率为 1 1 .1 % ,低于其它类型AML病人的HLA DR阳性率 (76 .3% ) ,P <0 .0 1。B系ALL中 ,CD34表达与FAB分型、起病时白细胞数、髓外侵润情况均无关 (P >0 .0 5 ) ;CD34-组婴幼白血病发生率 (1 7.6 % )高于CD34+ 组 (4 .2 % ) ,P <0 .0 5。结论　HLA DR阴性对于M3的诊断具有一定参考价值。     

Treatment of Inborn Errors of Metabolism

The results of a collaborative study of children treated on newborn mass-screening program in Japan are described. Forty-three cases of PKU, in which the dietary treatment was started between 9 to 35 days of life, were followed up, their ages ranging from 6 months to .6 years. DQ or IQ was found to be within normal range in all cases. As compared with IQ in untreated cases of PKU, an evident effect of early treatment was observed. Two of ten cases of hyperphenylalaninemia were found to be of the malignant type due to a defect in biopterin synthesis. Oral test of tetrahydrobiopterin to decrease of serum phenylalanine was thought to be clinically useful in the differential diagnosis of malignant hyperphenylalaninemia. Eight cases of galactosemia on the dietary treatment were followed up, their ages ranging from 6 months to 8 years. DQ or IQ was found to be within normal range in 7 of 8 cases. Five cases of maple syrup urine disease on the dietary treatment were followed up. DQ was within normal range in 3 of 5 cases. One died of sepsis at 39 days of life, and the other one showed lower IQ. A simple method for detecting hyperammonemia was described. The method requires only one drop of blood and takes only 15 minutes to complete. This new method is considered to be useful for routine, low-cost mass-screening of newborn infants for hyperammonemia. Newborn mass-screening program for phenylketonuria (PKU), maple syrup urine disease (MSUD), homocystinuria, histidinemia and galactosemia has been going on in Japan with the support of the Ministry of Health and Welfare since 1977. In parallel with this program, the collaborative study of children treated for these disorders has been started to evaluate the effects of early treatment. This investigation was made in eleven medical centers listed in Table 1 all over Japan. This paper describes a brief summary of the collaborative study.     

Unusual Cause of Persistent Impairment of Ventricular Function after Repair of Coarctation of the Aorta

In neonates with coarctation of the aorta, left ventricular function may be impaired due to an increased afterload and an associated endocardial fibroelastosis. Repair of the coarctation usually results in improvement in left ventricular function over the postoperative weeks. We report a patient in whom, despite successful repair of coarctation, left ventricular performance continued to deteriorate. Investigation revealed the unusual coincidental finding of anomalous left coronary artery from the right pulmonary artery.     

Treatment of percutaneous angioplasty of restenoses of coarctation and stenosis of bioprostheses in children]

The authors discuss the percutaneous balloon dilatation procedure and the results obtained in 10 children (age range: 2.5-13 years) over a 2 year period (April 1986-April 1988). Six cases of coarctation restenosis were observed and good clinical and hemodynamic results were noted in 2 cases, while in 4 cases the procedure was not totally successful. For the 4 cases of stenosis of bioprosthetic valves in right ventricular-to-pulmonary arterial conduits, good results were obtained with a significant reduction of the trans-stenotic gradient from 50 to 23 mmHg. While long-term effectiveness of the procedure is still uncertain, those encouraging preliminary results suggest that this procedure could be considered as an alternative treatment for coarctation restenosis and stenosis of bioprosthetic valves in right ventricular to pulmonary artery conduits.     

Significance of antenatal diagnosis of omphalocele

A comparison has been made between 16 infants with omphalocele treated between 1962 and 1975 (group A) and 22 treated between 1976 and 1989. In the latter group 11 antenatally detected cases (group C) were considered separately from the 11 cases diagnosed at birth (group B). Recent advances have reduced the mortality for neonates with omphalocele from 37.5% in group A to 18.2% in group B. However, despite antenatal diagnosis, maternal transport, and early perinatal care, a surprising increase in mortality (45%) was observed among neonates with omphalocele detected antenatally (group C). Seven cases in group C (60%) also had other lethal or potentially lethal multiple anomalies including trisomy 13 or 18, and it is probable that the high mortality in this group was a result to these associated anomalies. Before the introduction of antenatal diagnosis, most of these infants would have died before referral to a pediatric surgeon for treatment. In general, if omphalocele is an isolated lesion the prognosis for survival following postnatal surgical correction exceeds 90%; in such cases, antenatal diagnosis may potentially contribute to improved survival. However, the presence of other multiple and/or untreatable malformations in the group diagnosed antenatally is associated with a poor overall prognosis.     

The sound of silence: evolution of the object in the relationship of parents of two twins

This paper derives from a longer dissertation submitted for an MA in Psychoanalytic Observational Studies. Aspects of thinking about silence and significant contributions to the psychoanalytic and psychological research history are discussed in depth as a prologue to the discussion of a case in which the parents of twins were seen by the author in an attempt to encourage more listening as well as talking between the father and mother and with their children. Silence is seen as a significant internal sounding board through which the individual may listen to what others say, to himself, and to enable the birth to new thoughts. The review in depth of the literature on silence is applied to therapeutic work undertaken by the author with a couple one of whose twins was in psychotherapy. The author connects the significance of the absence of silence and the absence of toleration of silence in the couple with absence of the experience of being taken in, contained, and of the experience of being heard and listened to by internal parents.