Anaesthesia for liver transplantation in a patient with methylmalonic acidaemia

Liver transplantation is an accepted modality of treatment in some patients with inborn errors of metabolism. We present a child with methylmalonic acidaemia who had successful liver transplantation. The pathophysiology, medical and anaesthetic managements are discussed.     

Kainic acid-induced substantia nigra seizure in rats: behavior, EEG and metabolism

RATIONALE: In order to clarify the role of substantia nigra pars reticulata (SNr) upon the development of epileptic seizure, kainic acid (KA) was injected into a unilateral SNr. MATERIALS AND METHODS: Wistar rats weighing 250-350 g were used. A stainless-steel cannula and depth electrode were inserted stereotaxically into the left substantia nigra pars reticulata (SNr). At 7 days after surgery, 1.0 microg of KA was injected into the left SNr. Experiment 1: In eight rats, behavior and electroencephalograms (EEG) were continuously recorded for about 30 h, and intermittently monitored following 1 month. Experiment 2: Two hours after KA injection into SNr, rats demonstrated status epilepticus. Then, 100 microCi/kg of [(14)C]2-deoxyglucose (2-DG) was intravenously injected in seven rats, and the rats were processed for autoradiographic study. RESULTS: Changes in behavior and EEG: On EEG, a secondary generalized seizure status was observed at about 70 min after KA injection. In video, limbic seizure manifestations such as salivation were observed as a initial symptom and followed by rolling and generalized tonic seizures. [(14)C]deoxyglucose autoradiographic study demonstrated increased local cerebral glucose metabolism in the medial and lateral septal nucleus, substantia nigra, hippocampus, parietal cortex, piriform cortex, medial and lateral geniculate nucleus, anterodorsal, lateral and ventral nucleus of the thalamus, amygdala and midbrain reticular formation. SUMMARY: The result suggested that the substantia nigra played an important role in the secondary generalization in the substantia nigra seizure model due to the decreased function of the GABAergic projection system induced by an excessive epileptic excitation of SNr.     

Effect of grapefruit juice on cyclosporin A pharmacokinetics in pediatric renal transplant patients

Cyclosporin A (CsA) is an important immunosuppressant that is prone to numerous drug interactions. Grapefruit juice has been investigated, as a possible adjunct to CsA dosing in adult renal transplant recipients, to decrease CsA metabolism and reduce dosages. This study investigated this combination in pediatric renal transplant patients. Six stable pediatric renal transplant patients were entered into an open-label, four-period cross-over study in which patients were given their current CsA dose as either an oral solution (CsA-Sol) or a microemulsion (CsA-ME). In addition, drugs were administered concurrently with water or grapefruit juice. Steady-state pharmacokinetic profiles were taken during each of the four periods. Following the concurrent administration of grapefruit juice, CsA whole-blood 12-h trough levels were significantly increased during CsA-Sol dosing. Furthermore, the CsA elimination rate constant was significantly reduced during the same period. After CsA-ME dosing, no differences in CsA pharmacokinetics were found between concurrent water or grapefruit ingestion. Grapefruit juice co-administration reduced the production of CsA metabolites, AM1 and AM9, during CsA-Sol dosing. No changes in CsA metabolite production were found when patients were given CsA-ME with grapefruit juice as compared with water. Hence, alterations in CsA absorption and elimination occur with concurrent grapefruit juice ingestion when stable pediatric renal transplant patients are taking the oral CsA solution, but not the microemulsion formulation. These changes may be mediated by alterations in intestinal or hepatic metabolism, or drug absorption. The effect of grapefruit juice on CsA absorption is not readily predictable in these patients.     

儿童期癌症长期存活者糖代谢和脂代谢异常的调查分析

目的探讨儿童期癌症长期存活者糖代谢异常发生率及脂代谢变化,为采取干预措施提供依据。方法选择2006年3月-2008年4月新乡医学院第一附属医院肿瘤科门诊接受长期随访的50例生存期在5 a以上儿童期癌症患者纳入研究(长期生存组),其初诊癌症年龄为0.6~13.7岁(中位年龄5.7岁),入组时已接受随访的时间2.9~28.6 a,随访中位年数12.4 a,入组年龄11.6~32.3岁,中位年龄13.2岁。其中男24例,女26例。随机选取同期在新乡医学院第一附属医院进行健康体检的50例年龄、性别与之相匹配的健康人为健康对照组。测量二组身高、体质量指数(BMI)、腰围,同时检测二组血脂、血糖、空腹血浆胰岛素、口服糖耐量试验,比较二组超体质量或肥胖、高血脂、异常糖耐量(IGT)、糖尿病(DM)、高空腹血浆胰岛素(HI)发生率。结果二组超体质量/肥胖及BMI无统计学差异,长期生存组腰围/身高比值明显高于健康对照组[(0.49±0.07)vs(0.46±0.05)P<0.05],IGT、HI发生率明显高于健康对照组(P<0.05,0.01)。与健康对照组比较,长期生存组高密度脂蛋白较低、总胆固醇和空腹血糖较高[(1.2±0.3)vs(1.40±0.39),(4.8±0.7)vs(4.2±0.8),(5.1±0.8)vs(4.8±0.5)],但无统计学意义。结论儿童期癌症长期存活者糖代谢异常伴随脂代谢异常发生率高,必须予以重视,并及早给予预防。     

Impact of subdermal norgestrel on hepatic acyl-coenzyme A:cholesterol- acyltransferase (ACAT) activity: possible antiatherogenic effect

The impact of subdermally placed ethinyl estradiol, norgestrel, and the combination of the two on cholesterol metabolism as measured by hepatic acyl:cholesterol-acyltransferase (ACAT) activity was examined in the rat model. A total of 48 rats were assigned to one of 6 groups, receiving either 0.1 mg or 1.0 mg of ethinyl estradiol daily, 1.0 or 10 mg of norgestrel daily, and combinations of either 0.1 mg ethinyl estradiol/1.0 mg norgestrel or 1.0 mg ethinyl estradiol/10 mg norgestrel daily. All drugs were administered through subdermally placed time release capsules. The administration of norgestrel only in either 1.0 mg or 10 mg resulted in significantly lower rates of ACAT activity (0.77 ± 0.566 and 0.91 ± 0.239 pmol/mg/min, respectively). The combination of 1.0 ethinyl estradiol and 10 mg norgestrel resulted in a significant increase in ACAT activity to 2.17 ± 0.873. This combination also resulted in significantly greater weight loss at the conclusion of treatment [247.83 ± 6.2 g (pre) vs. 205.50 ± 10.6 (post)]. There were no other differences in ACAT activity between groups and no other differences in weight, both between groups and pre- and post-treatment within groups. In summary, subdermally placed norgestrel resulted in a significant lowering of ACAT activity not seen with either administration of ethinyl estradiol alone or the combination of ethinyl estradiol and norgestrel in doses ranging from 0.1 to 1.0 mg of ethinyl estradiol and 1.0 to 10.0 mg of norgestrel. Significantly increased ACAT activity for the combination of 1.0 ethinyl estradiol and 10 mg norgestrel over either ethinyl estradiol or norgestrel alone or a lower dose combination suggests a dose-related threshold and drug-drug interaction for this effect. These results suggest that subdermally placed norgestrel may result in significantly lower ACAT activity and may have a potential role as an antiatherogenic treatment.     

肝病血瘀证与血清球蛋白的关系

分析78例慢性肝病病人,发现血清球蛋白及γ-球蛋白在肝病血瘀证病人中显著增高,活血化瘀治疗后,随着血瘀证临床表现的改善,血清球蛋白及γ-球蛋白也显著下降。说明血清球蛋白及γ-球蛋白作为肝病血瘀证的客观化指标,其可靠性、特异性、敏感性均高。其中γ-球蛋白的特异性显著优于血清球蛋白。     

Cerebral energy metabolism in insulin induced hypoglycemia in newborn piglets: in vivo31P-nuclear magnetic resonance spectroscopy

The effect of insulin induced hypoglycemia on cerebral energy metabolism was examined in four newborn piglets. Cerebral energy metabolism was assessed using in vivo ³¹P-nuclear magnetic resonance spectroscopy. It was demonstrated that the normal level of phosphocreatine/inorganic phosphate (PCr/Pi), an indicator of phosphorylation potential, was maintained at a blood glucose level of 40 mg/dL or above, whereas when blood glucose was reduced to less than 40 mg/dL, PCr/Pi rapidly decreased in parallel with this. Below the critical blood glucose level of 40 mg/dL, a positive correlation (y = 0.02x + 0.632; r = 0.668; P < 0.001) existed between blood glucose and PCr/Pi. In the present investigation, a reduction of blood glucose level to 20 mg/dL or lower resulted in a PCr/Pi of less than 1, indicating a state of cerebral energy failure. The intracellular pH (pHi) was 7.08 ± 0.05 at the onset and 7.15 ± 0.07 in the hypoglycemic state, indicating no significant difference between the two groups. The present study has clarified that cerebral energy failure occurs when the blood glucose level is about 20 mg/dL or lower. The critical point of blood glucose exists to maintain brain energy metabolism.     

Sibling cases of a degenerative neurological disease associated with hypocupraemia and hypobetalipoproteinaemia

We describe two siblings, a boy and his younger sister, with degenerative neurological disturbances, hypocupraemia and hypobetalipoproteinaemia. The neurological features in both cases were developmental delay, dysarthria, hyperkinetics with an attention deficit, dysdiadochokinesis, night blindness, myoclonic jerks and convulsions. Their serum cooper levels did not increase despite administration of copper sulphate both orally or intravenously. The copper contents of the cultured fibroblasts in the patients were 1.5-fold that of controls.Although neurological disorders associated with abnormal copper metabolism and inherited in an X-linked manner have been previously reported, this is the first report of a neurodegenerative disease concurrent with abnormal copper metabolism and hypobetalipoproteinaemia.     

Water, energy and early postnatal growth in preterm infants

Non-invasive methods, including stable isotope techniques, indirect calorimetry, nutritional balance and skinfold thickness, have given a new insight into early postnatal growth in neonates. Neonates and premature infants in particular, create an unusual opportunity to study the fluid and metabolic adaptation to extrauterine life because their physical environment can be controlled, fluid and energy balance can be measured and the link between metabolism and the energetics of their postnatal growth can be assessed accurately. Thus the postnatal time course of total body water, heat production, energy cost of growth and composition of weight gain have been quantified in a series of "healthy" low-birth-weight premature infants. These results show that total body water is remarkably stable between postnatal days 3-21. Energy expenditure and heat production rates increase postnatally from mean values of 40 kcal/kg/day during the first week to 60 kcal/kg/day in the third week. An apparent energy balance deficit of 180 kcal/kg can be ascribed to premature delivery. The cost of protein metabolism is the highest energy demanding process related to growth. The fact that nitrogen balance becomes positive within 72 h after birth places the newborn in a transitional situation of dissociated balance between energy and protein metabolism during early postnatal growth: skinfold thickness, dry body mass and fat decrease, while there is a gain in protein and increase in supine length. This particular situation ends during the second postnatal week and soon thereafter the rate of weight gain matches statural growth. The goals of the following review are to summarize data on total body water and energy metabolism in premature infants and to discuss how they correlate with physiological aspects of early postnatal growth