Alpha thalassaemia mental retardation (ATR-X): an atypical family

A novel form of severe, X linked mental retardation associated with alpha thalassaemia (ATR-X syndrome) has recently been described. Two affected cousins are described, one of whom has an unusually mild haematological phenotype. HbH inclusions, which are the hallmark of this disease, were only detected in the peripheral red blood cells after repeated observations.     

Disproportionate short stature after cranial irradiation and combination chemotherapy for leukaemia

The effect of combination chemotherapy and cranial irradiation on final height and body proportions was retrospectively examined in a cohort of 142 children treated for acute lymphoblastic leukaemia (ALL). Eighty four children (48 girls, 36 boys) received 24 Gy cranial irradiation and 58 (35 girls, 23 boys) 18 Gy. None had received testicular or spinal irradiation. A significant reduction in standing height SD score from diagnosis to final height was seen in all groups. Of the 109 children in whom sitting height measurements were available, 88 (81%) had relatively shorter backs than legs and in 25 (23%) this disproportion was of a marked degree. After mathematical correction for sitting height loss there was no longer a significant reduction in standing height SD score at final height in all except the 24 Gy group of girls. These data suggest that disproportion is a common finding after treatment for ALL and that, at least in some children, much if not all of the height loss seen is due to a reduction in sitting height. Possible explanations for this disproportion include a disturbance of puberty or an effect of chemotherapy on spinal growth, or both.     

Behavioural effects of phenobarbitone and phenytoin in small children

Mothers of 56 children under 2 years old taking phenobarbitone and mothers of 55 children taking phenytoin recorded on questionnaires changes they had noted in the children's behaviour 3 and 9 weeks after starting the drug. Severe behavioural disturbance was noted by many, but the pattern and incidence was similar to that recorded by the mothers of 50 children starting a placebo, and we attribute it to the effect of a recent hospital admission. There was a small improvement in the behaviour of 20% of children who had been taking phenobarbitone for a year when they stopped it, but in this age group the disturbance caused by phenobarbitone did not appear to have been great.     

Ranitidine (Zantac) syrup versus Ranitidine effervescent tablets (Zantac) EFFERdose) in children: a single-center taste preference study

BACKGROUND: The histamine H(2) receptor antagonist ranitidine is US FDA-approved for the treatment of gastroesophageal reflux disease and healing of erosive esophagitis in children >or=1 month of age. A low-dose strength of ranitidine is now available in a citrus-flavored 25 mg effervescent tablet (dissolved in 5 mL of water); this formulation was developed to facilitate use in infants and smaller children. Ranitidine syrup is available in a peppermint-flavored 15 mg/mL formulation. OBJECTIVE: To compare taste preferences for ranitidine (Zantac) syrup and ranitidine effervescent tablets dissolved in water (Zantac EFFERdose) in healthy children aged 4-8 years and their adult caregivers. STUDY DESIGN AND METHODS: A randomized, single-blind, crossover, taste test trial was conducted in 102 children and 102 parents/legal guardians. All subjects received a single 45 mg dose of each formulation. After tasting both preparations children were asked: "Now that you have tasted both medicines, which one of these medicines do you think tastes better?" Adults were asked four questions to assess whether they would administer the medication to the children. RESULTS: Seventy-one percent (72/102) of the children preferred the taste of the ranitidine effervescent tablets compared with 29% (30/102) who preferred the syrup (p < 0.001). The majority of adults (71%) responded that they would prefer to administer the effervescent formulation based on taste. Adverse events consistent with product labeling were mild and were reported in four children and three adults: headache (n = 3), drowsiness (n = 1), abdominal pain/cramps (n = 2), and bloating/gas (n = 1). CONCLUSION: The taste of the ranitidine effervescent formulation dissolved in water is preferred over the ranitidine syrup. Better taste acceptance may facilitate ease of administration and compliance in pediatric patients.     

Close mapping of the focal non-epidermolytic palmoplantar keratoderma (PPK) locus associated with oesophageal cancer (TOC)

Focal non-epidermolytic palmoplantar keratoderma (PPK or palmoplantar ectodermal dysplasia type III) is associated with oesophageal cancer in three families: two large pedigrees located in Liverpool, UK and in the midwestern American states and one smaller family from Germany. In these families, the PPK is inherited as autosomal dominant and has a late onset, usually manifesting between 7 and 8 years of age. The disease is characterised by thickening of the pressure areas of the soles, but is not restricted to the feet and also presents with oral leukokeratosis and follicular hyperkeratosis. The disease locus [previously termed the "tylosis oesophageal cancer gene' (TOC) locus] has been mapped to 17q23-qter by linkage analysis. This region is located telomeric to the keratin 16 gene, in which mutations have been identified in focal PPK families who show no increased cancer risk. We describe the close mapping of this locus to the interval between AFMb054zf9 and D17S1603 using haplotype analysis of additional Genethon markers in the region and show that although the American family is unlikely to be related to either of the other two, the UK and German pedigrees may share a common descent. This work provides a basis for positional cloning and candidate gene analysis in order to identify a gene that may be involved in familial oesophageal cancer.      

Spectrum of mutations in the fumarylacetoacetate hydrolase gene of tyrosinemia type 1 patients in northwestern Europe and Mediterranean countries

Hereditary tyrosinemia type 1 (HT1) is a rare metabolic disease caused by a deficient activity of the enzyme fumarylacetoacetase (FAH). To investigate the molecular heterogeneity of tyrosinemia, the geographic distribution and the genotype–phenotype relationship, we have analyzed the FAH genotype of 25 HT1 patients. Mutation screening was performed by PCR amplification of exons 1-14 of the FAH gene, followed by SSCP analysis and direct sequencing of the amplified exons. Fourteen different mutations were found, of which seven were novel, viz. Three missense mutations (G158D, P261L, F405H), a deletion of three nucleotides causing a deletion of serine (DEL366S) and three splice site mutations: IVS2+1(g-t), IVS6-1(g-c), IVS8-1(g-c). The splice site mutations IVS6-1(g-t) and IVS12+5(g-a) were frequently found in countries around the Mediterranean and northerwestern Europe, respectively. No clear correlation between the genotype and the three major HT1 subtypes could be established. Hum Mutat 12:19–26, 1998. © 1998 Wiley-Liss, Inc.     

消旋棉酚拆分的研究——Ⅱ.手性α-甲基苯乙胺及α-甲基苄胺为拆分剂

本文报道用中压柱色谱快速分离S或R-α-甲基苯乙胺及S或R-α-甲基苄胺缩(±)-棉酚的方法,可得光学活性胺缩(+)或(一)-棉酚非对映体,经水解分别得到(+)或(一)-棉酚。并证明胺缩光学活性棉酚非对映体之间有互相转化的性质,此特性可利用于棉酚对映体的转化。