Involvement of deprivation and environmental lead in neural tube defects: a matched case-control study

OBJECTIVE: To analyse the prevalence of neural tube defects in small geographical areas and seek to explain any spatial variations with reference to environmental lead and deprivation. SETTING: The Fylde of Lancashire in the north west of England. DESIGN: Cases were ascertained as part of a prospective survey of major congenital malformations in babies born in the Fylde to residents there between 1957 and 1981. A matched case-control analysis used infants with cardiovascular system, alimentary tract, and urinary system malformations as controls. Conditional logistic regression was used to assess the effects of more than 10 micrograms/l lead in drinking water and the Townsend deprivation score. RESULTS: The prevalence of neural tube defects in 1957-73 was higher in Blackpool, Fleetwood, and North Fylde, whereas the three control groups showed no significant spatial variation. In 1957-81 mothers living in electoral wards with either a higher proportion of houses with more than 10 micrograms/l lead in the water or a higher deprivation score had a greater risk of having a baby with a neural tube defect. For spina bifida and cranium bifidum alone, this was also true. For anencephaly, deprivation was less important although the effect of lead was still seen. In some neural tube defects, lead may act independently of other possible factors associated with deprivation. It seemed unlikely that lead levels changed significantly during the survey. The percentage of houses with 10 micrograms/l or more of lead in the water in 1984-5 was similar to that found in Great Britain 10 years previously. CONCLUSION: There is evidence to suggest that lead is one cause of neural tube defects, especially anencephaly. This could link the known preventive actions of hard water and folic acid. Calcium is a toxicological antagonist of lead. One cause of a deficiency of folic acid is impaired absorption secondary to zinc deficiency, which may be produced or exacerbated by lead.     

Response of sensitive and resistant IgM immunocytomas to cis-diamminedichloroplatinum(II) does not correlate with the platination level or with the formation or removal of DNA adducts

 An IgM immunocytoma cell line sensitive to cis-diamminedichloroplatinum(II) (CDDP) and a subline with acquired resistance were grown in LOU/M rats. In a previous study with such rats that had been treated with a high dose of CDDP (10 mg/kg) the tumors did not show differences in cellular platinum content or DNA-adduct levels, either immediately after treatment or 24 h later. Recently, this high dose was found to overcome resistance. Therefore, the study was repeated with a 10-fold lower dose (1 mg/kg, i.v.). At 1 and 24 h after treatment, tumor and kidney tissue were assayed for cellular platinum (atomic absorption spectroscopy, AAS) and DNA platination (immunochemical detection of the four CDDP-DNA adducts). The results were compared with previous data. All tissues showed a linear response to dose with regard to platinum uptake as well as adduct formation, with no quantitative difference being seen between the tumors. Also the relative occurrence of the four adducts was very similar. Between 1 and 24 h, in tumors a substantial decrease occurred in both platinum content and adduct level; the kidneys showed little reduction, if any. At the lower CDDP dose a somewhat larger loss of platinum and removal of DNA adducts was observed for the resistant tumor, but these differences could be explained by “dilution”, as this tumor continues to grow after low-dose treatment (about 20% within 24 h). Since the strong difference observed between the tumors in sensitivity to CDDP cannot be attributed to differences in CDDP uptake, efficiency of adduct formation, or repair capability, other mechanisms are held responsible. Received 10 August 1995 / Accepted: 14 August 1996     

Tuberous sclerosis complex and Wolff-Parkinson-White syndrome

This report highlights the association between tuberous sclerosis and Wolff-Parkinson-White syndrome. Ten patients with concurrent diagnoses of Wolff-Parkinson-White syndrome and tuberous sclerosis were identified. Wolff-Parkinson-White syndrome presented early in life, nine cases being diagnosed in the first year. Eight of the 10 cases were male. In eight cases, the syndrome was associated with supraventricular tachycardias, and in nine with cardiac rhabdomyomata. One child died from cardiac failure secondary to obstruction of the left ventricular outflow tract by a rhabdomyoma. Five of nine survivors showed resolution of Wolff-Parkinson-White syndrome on follow up. The accessory pathway was localised in nine patients from surface electrocardiograms: six children had left sided pathways and three had right sided pathways.     

Risk factors for respiratory syncytial virus associated apnoea

Respiratory syncytial virus (RSV) infections are characterized by upper or lower respiratory tract symptoms including bronchiolitis and pneumonia. Apnoea may be the first sign of disease in children with RSV infection. The aims of this study were the identification of independent risk factors for RSV associated apnoea and the prediction of the risk for mechanical ventilation in children with RSV associated apnoea. Medical records of children younger than 12 months of age admitted with RSV infection between 1992 and 1995 to the Sophia Children's Hospital, were reviewed. Demographic parameters, clinical features and laboratory parameters (SaO₂, pCO₂ and pH) were obtained upon admission and during hospitalization. Children with and without apnoea were compared using univariate and multivariate logistic and linear regression analysis. One hundred and eighty-five patients with RSV infection were admitted of whom 38 (21%) presented with apnoea. Patients with apnoea were significantly younger, had a significantly lower temperature, higher pCO₂ and lower pH and had on chest radiographs also more signs of atelectasis. The number of patients admitted to the ICU because of mechanical ventilation and oxygen administration was significantly higher in children with RSV associated apnoea. Apnoea at admission was a strong predictor for recurrent apnoea. The relative risk for mechanical ventilation increased with the number of episodes of apnoea: 2.4 (95% CI 0.8 – 6.6) in children with one episode of apnoea (at admission) versus 6.5 (95% CI 3.3 – 12.9) in children with recurrent episodes of apnoea. Conclusions Age below 2 months is the strongest independent risk factor for RSV associated apnoea. Apnoea at admission increases the risk for recurrent apnoea. The risk for mechanical ventilation significantly increases in children who suffer from recurrent apnoea. Received: 12 May 1997 / Accepted in revised form: 22 August 1997     

Blood-brain barrier and blood volume imaging of cerebral glioma using functional CT: A pictorial review

Five cases of cerebral glioma are presented here that illustrate the benefit of functional CT imaging of blood-brain barrier permeability and cerebral blood volume. Functional CT uses Patlak analysis of a single location dynamic sequence to extract physiological information that is useful clinically in the assessment of cerebral gliomas. Functional CT offers distinct advantages over other functional modalities including clearer delineation of tumour, tumour grading, measurement of tumour activity and monitoring response to therapy.     

The rat vertex-middle latency auditory-evoked potential as indicator of anaesthetic depth: a comparison with evoked-reflex testing

We investigated whether components from the rat Vx-MLAEP could be used to assess depth of anaesthesia induced by propofol. Propofol decreased MLAEP amplitudes and increased latencies. We propose that the P(16)-N(22) wave in the rat MLAEP is similar to the human P1, and that recovery of this wave during propofol anaesthesia correlates with behavioural measures of the regaining of consciousness.     

他汀治疗儿童家族性高胆固醇血症的有效性和安全性——随机对照试验

背景：家族性高胆固醇血症儿童往往存在内皮功能异常和颈动脉内膜中层厚度（intima—media thickness，IMT）增加，预示这类患儿未来有可能早发动脉粥样硬化性疾病。虽然针对这种疾病的病因干预治疗已开展十余年，但是目前尚无研究对儿童应用降胆固醇药物的长期疗效和安全性进行评价。 目的：评价家族性高胆固醇血症儿童应用普伐他汀（pravastatin）治疗2年的疗效及安全性。 设计：本随机、双盲、安慰剂对照试验于1997年12月7日至1999年10月4日入选儿童，随访2年。 地点及参试者：214名8～18岁家族性高胆固醇血症儿童均来自荷兰一家医疗救治中心。 干预：限制患儿脂质摄入并鼓励开展日常体育锻炼，随后患儿随机分配接受20～40mg/d普伐他汀治疗（n=106）或安慰片剂治疗（n=108）。主要观察指标：疗效的评价指标是2年后两组患儿颈动脉IMT平均值的变化；安全性的评价指标为2年后患儿生长发育成熟情况、激素水平以及肌肉和肝脏酶的变化。 结果：与基线相比，普伐他汀组颈动脉IMT呈现出减小的趋势（均值[SD]，-0．010[0．048]mm；P=0．049），而安慰剂组呈现出增厚的趋势（均值[sD]，＋0．005[0．044]mm；P=0．28）。两组问IMT的均值（sD）变化（0．014[0．046]mm）具有品著性（P=0．02）。另外，与安慰剂组相比，普伐他汀组低密度脂蛋白胆固醇的平均水平显著降低（分别为-24．1％和＋0．3％；P〈0．001）。两组间生长发育、肌肉或肝脏酶、内分泌功能指标、Tanner阶段评分、月经初潮和睾丸体积均无差异。 结论：采用普伐他汀治疗家族性高胆固醇血症患儿2年后颈动脉粥样硬化明显减退，药物对生长发育、性器官成熟、激素水平和肌肉、肝脏组织无副作用。     

The stepping response in early infancy

Postnatally, the stepping response can be elicited right after birth, but soon diminishes and disappears by about 2-3 months of age. It is still not clear if the disappearance of the response is caused by gradual maturation of the central nervous system, environmental factors, or biomechanical factors such as added body weight and/or increased muscle mass of the legs. This clinical study assessed the stepping response in a group of healthy infants (n = 58) at the age of 6 weeks: 37 born preterm and corrected for gestational age. Quantitative measures of stepping response were obtained together with the qualitative measures of behavioural state and the distribution of active and passive muscle power of the legs. Mechanical factors were studied by dividing the infants according to their birth weight status, and calculating the ponderal index (PI), leg volume (LV), and weight gain of each group. Preterm infants show more stepping responses, more muscle power discrepancies, and different leg volumes than their full-term counterparts. In addition, our results reported significant relationship between gestational age and relative birth weight on the manifestation of stepping response. Within the preterm group the responses lingered longer in infants with shorter gestational ages and in those with lower birth weight status. Consequently, this study suggests that environmental experience and the time of birth of the infants play a more significant role than maturation and mechanical factors in the manifestation of the infantile stepping response.     

Risperidone versus haloperidol in psychotic patients with disturbing neuroleptic-induced extrapyramidal symptoms: a double-blind, multi-center trial

BACKGROUND: A randomized, double-blind, multi-center trial was started to compare the severity of extrapyramidal symptoms (EPS) during risperidone and haloperidol treatment in schizophrenic patients who had disturbing EPS during their previous neuroleptic treatment. Additional objectives of this trial were comparing the antipsychotic effectiveness of the two treatments and the use of antiparkinsonian medication. METHODS: Effects of flexible doses of risperidone and haloperidol were compared in 77 psychotic patients (83% with chronic schizophrenia) with disturbing neuroleptic-induced EPS (risperidone 40 patients, haloperidol 37). The trial was completed by 47 patients: 25 in the risperidone group (12 women, 13 men), and 22 in the haloperidol group (10 women, 12 men). RESULTS: An adequate antipsychotic effect was obtained in most patients by both treatments. The primary aim of this trial was comparing parkinsonism measured with the extrapyramidal syndrome rating scale (ESRS) during treatment with risperidone and haloperidol. Two primary parameters were selected: the change from baseline to the worst score during treatment of ESRS II (parkinsonism) and ESRS VI (clinical global impression of severity of parkinsonism). The CGI of severity of parkinsonism was better with risperidone (P=0.025), while the parkinsonism total score tended to be better with risperidone (P<0. 10). Before the double-blind treatment, 34 (of the 77) had used antiparkinson medication (risperidone 18, haloperidol 16). During the double-blind treatment phase, 21 patients had used antiparkinson medication (risperidone 11, haloperidol 10). The larger reduction of parkinsonism in the risperidone group was not due to a difference in the use of anti-parkinsonian medication. CONCLUSIONS: In this group of schizophrenic patients with disturbing EPS during previous neuroleptic treatment, a stronger reduction of parkinsonism was observed with risperidone than with haloperidol.