Dose-response study of oral 2,3-dimercaptosuccinic acid in children with elevated blood lead concentrations

2,3-Dimercaptosuccinic acid (DMSA) is an orally effective orphan drug that is more specific and has a wider therapeutic index than other currently available drugs used for lead intoxication. Its investigational use in the United States has been limited to the treatment of men with occupational plumbism. Twenty-one children with blood lead concentrations of 31 to 49 micrograms/dl, who also had a positive calcium disodium edetate (CaNa2EDTA) mobilization test result, were hospitalized for 7 days. Fifteen children were randomly assigned to three groups that received either 350, 700, or 1050 mg/m2/day, respectively, of DMSA in three divided doses daily. A fourth group of six children received conventional treatment with 1000 mg/m2/day of intravenously administered CaNa2EDTA in two divided doses daily. The 1050 mg/m2/day dose of DMSA was significantly more effective than lower doses of DMSA or intravenously administered CaNa2EDTA in reducing blood lead levels and restoring erythrocyte delta-aminolevulinic acid dehydratase activity. Intravenously administered CaNa2EDTA significantly increased the urinary excretion of several essential minerals (zinc, copper, iron, and calcium), whereas DMSA did not. The DMSA was well tolerated and appears extremely promising as a drug that will simplify the management of childhood lead poisoning.     

Update on the clinical management of childhood lead poisoning

Childhood lead poisoning is still an enormous public health issue in the United States, affecting thousands of children and their families. New evidence suggests that even very low blood lead levels, less than 10 microg/dL, can be associated with neurologic injury. This article discusses characteristics of children at high risk for lead poisoning, unusual sources of lead contamination, and new aspects of lead's pathophysiology. It includes current thinking on the clinical management and prevention of childhood lead poisoning.     

二巯基丁二酸治疗儿童铅中毒的研究进展

二巯基丁二酸（DMSA）作为口服驱铅药物在国外已广泛用于临床。由于依地酸二钠钙（CaNa2-EDTA）需静脉滴注给药,有一定的肾毒性,且治疗过程中同时增加了尿中锌、铜、钙等元素的排出。而DMSA口服给药驱铅效果优于CaNa2-EDTA,尤其对脑等软组织中的铅有较强的清除能力,可改善铅毒性所致血液生化指标的异常,治疗过程中不良反应少,且相对选择性驱铅对其他元素的干扰较小,因此DMSA已作为儿童驱铅治疗的首选药物。目前DMSA是否推荐用于治疗血铅水平≤450μg／L的患儿成为国外研究的热点。我国卫生部2006年2月颁发的《儿童高铅血症和铅中毒分级和处理原则（试行）》指出,儿童血铅水平在采用静脉血复测后仍然高于或等于250μg／L,且驱铅试验阳性者需进行药物驱铅治疗,首选药物为DMSA。该文综述了近年来DMSA治疗儿童铅中毒的临床及动物实验方面的一些研究进展。     

Deleading dilemma: pitfall in the management of childhood lead poisoning

Deleading is a dangerous process which, if improperly done, can result in acute lead intoxication. The following case report illustrates what happened to an already-lead-poisoned child's lead level when he was not excluded from his apartment during deleading. Supportive evidence is provided from 12 additional cases recently seen by the same pediatric practice. The issues behind the failure of these families to vacate their apartments during deleading are discussed, and the need for lead-poisoning prevention programs to address these issues, particularly that of providing alternative shelter during deleading, is stressed. Society should adequately fund such programs so that they become a reality.     

Postural sway analysis of a teenager with childhood lead intoxication--a case study.

We had an opportunity to study a 15-year-old boy, evaluating the long-term effect of early childhood lead (Pb) poisoning on the maturation of postural balance. Postural balance (or sway) was quantified using a microprocessor-based Force Platform System along with four postural tasks specifically designed to indirectly challenge and/or minimize the effect of vision, proprioception and vestibular systems relevant for postural stability. The Pb-intoxicated patient showed increased postural sway compared to those of non-poisoned young adults and a 14-year-old boy for postural tasks requiring input from higher centers. A review of historical information and results of the physical and neurological examinations did not reveal an alternative explanation for this patient's postural sway abnormalities. These responses are also comparable to those noted in younger children with chronic Pb-exposure histories. In summary, this case study gives suggestive evidence that early excessive exposure to Pb can have long-term, detrimental neurological effects as reflected by postural stability. Measurement of postural balance appears to be a sensitive research methodology to assess subclinical neurological effects of remote lead intoxication.     

Detection and management of childhood cholesteatoma.

Childhood cholesteatoma is an aggressive disease that demonstrates higher rates of recidivism than its adult counterpart. The priorities in ideal management include total removal, followed by hearing restoration, followed by preserving the ear anatomy. Especially in children, one must endeavor to preserve ear anatomy if it does not jeopardize total removal of cholesteatoma. Absolute indications for CWD surgery include an only-hearing ear, a severely destroyed posterior canal wall, an extremely contracted mastoid, and matrix overlying a semicircular canal fistula. Reasons for staging childhood cholesteatoma include suspected residual disease, uncertainty about total removal of cholesteatoma, severe mucosal disease, and CWU procedures in which the cholesteatoma has diffusely invaded the bone. Adequate long-term follow-up is imperative. Patients and their families should be reminded frequently of the importance of close follow-up because recidivism is frequent. Successful management of cholesteatoma in children does not involve a rigid, "one-way" approach. The surgeon must be flexible and capable of employing the most appropriate procedure for the patient.     

Advancing the management of childhood epilepsies

Childhood epilepsies comprise a heterogeneous group of disorders and syndromes that vary in terms of severity, prognosis and treatment requirements. Effective management requires early, accurate recognition and diagnosis, and a holistic approach that addresses each individual's medical and psychosocial needs within the context of their overall health status and quality of life. With increasing understanding of underlying aetiologies, new approaches to management and treatment are emerging. For example, genetic testing is beginning to provide a tool to aid differential diagnosis and a means of predicting predisposition to particular types of epilepsy. Despite the availability of an increasing number of antiepileptic drugs (AEDs) – due not only to the development of new AEDs, but also to changes in regulatory requirements that have facilitated clinical development – seizure control and tolerability continue to be suboptimal in many patients, and there is therefore a continuing need for new treatment strategies. Surgery and other non-pharmacological treatments (e.g. vagus nerve stimulation, ketogenic diet) are already relatively well established in paediatric epilepsy. New pharmacological treatments include generational advances on existing AEDs and AEDs with novel modes of action, and non-AED pharmacological interventions, such as immunomodulation. Emerging technologies include novel approaches allowing the delivery of medicinal agents to specific areas of the brain, and ‘closed-loop’ experimental devices employing algorithms that allow treatment (e.g. electrical stimulation) to be targeted both spatially and temporally. Although in early stages of development, cell-based approaches (e.g. focal targeting of adenosine augmentation) and gene therapy may also provide new treatment choices in the future.     

Electroneurostimulation for the management of bladder bowel dysfunction in childhood

Both non-invasive and invasive electroneurostimulation (ENS) modalities for bladder bowel dysfunction have been studied and reported in children. A summary of the proposed mechanism of actions and the more commonly used and recently reported techniques and outcomes are described. This includes transcutaneous electrical nerve stimulation, functional electrical nerve stimulation, intravesical electrical nerve stimulation, percutaneous tibial nerve stimulation and sacral neuromodulation in conditions including overactive bladder, enuresis, dysfunctional voiding, constipation, combined bladder bowel dysfunction and neuropathic bladder and bowel dysfunction. There is a need for further high quality randomised trials as well as long-term outcomes to establish whether ENS is able to alter the long-term trajectory for an individual child with bladder bowel dysfunction.     

Controlled trial of azathioprine in treatment of steroid-responsive nephrotic syndrome of childhood.

A controlled trial of azathioprine treatment of steroid-responsive frequent-relapsing nephrotic syndrome of childhood failed to show a therapeutic effect on the stability of remission after withdrawal of corticosteroid treatment.     

纸片法筛查儿童铅中毒的可行性研究

目的　建立一种简便、快速、经济、符合我国国情的儿童铅中毒筛查方法。方法　在纸片法检测血铅的方法已经建立的基础上 ,选择 15 8例 1～ 7岁的儿童 ,同时采集静脉血和手指末梢血进行血铅分析 ,以鉴定两种检测方法的相关性。结果　 15 8例静脉血和末梢血纸片法血铅浓度的相关系数达 0 86 89,P <0 0 1。以静脉血铅 10 0和 2 0 0 μg/L为标准 ,纸片法的阳性率分别为 87 3%和10 0 % ;假阴性率分别为 15 3%和 0 ;假阳性率分别为 7 7%和 0。结论　末梢血纸片法筛查儿童铅中毒是可行的 ,在采血过程中避免污染 ,严格按操作规程进行是关键