A safety and pharmacokinetic study of intravenous natalizumab in patients with MS

A phase 1, randomized, placebo-controlled, five-level dose escalation safety and tolerability and pharmacokinetic study of a single IV dose of natalizumab was performed. Doses of 0.03 to 3.0 mg/kg natalizumab or placebo were studied in 28 stable relapsing-remitting or secondary-progressive MS. All doses were safe and well tolerated in MS. Serum concentrations of natalizumab are detectable for 3 to 8 weeks after a single 1- or 3-mg/kg IV dose and justify controlled efficacy studies.     

Fatal meningoencephalitis due to Bacillus anthracis

Abstract: We report the first case of fatal anthrax meningoencephalitis in Hong Kong over the past 60 years. A 13 year-old boy presented with right lower quadrant pain, diarrhoea and progressive headache. Lumbar puncture yielded gram positive bacilli initially thought to be Bacillus cereus, a contaminant. He was treated with ampicillin and cefotaxime, but died 3 days after hospitalization. The organism isolated from blood and cerebrospinal fluid was later identified as Bacillus anthracis.     

Fetal stroke and cerebrovascular disease: Advances in understanding from lenticulostriate and venous imaging,alloimmune thrombocytopaenia and monochorionic twins

Fetal stroke is an important cause of cerebral palsy but is difficult to diagnose unless imaging is undertaken in pregnancies at risk because of known maternal or fetal disorders. Fetal ultrasound or magnetic resonance imaging may show haemorrhage or ischaemic lesions including multicystic encephalomalacia and focal porencephaly. Serial imaging has shown the development of malformations including schizencephaly and polymicrogyra after ischaemic and haemorrhagic stroke. Recognised causes of haemorrhagic fetal stroke include alloimmune and autoimmune thrombocytopaenia, maternal and fetal clotting disorders and trauma but these are relatively rare. It is likely that a significant proportion of periventricular and intraventricular haemorrhages are of venous origin. Recent evidence highlights the importance of arterial endothelial dysfunction, rather than thrombocytopaenia, in the intraparenchymal haemorrhage of alloimmune thrombocytopaenia. In the context of placental anastomoses, monochorionic diamniotic twins are at risk of twin twin transfusion syndrome (TTTS), or partial forms including Twin Oligohydramnios Polyhydramnios Sequence (TOPS), differences in estimated weight (selective Intrauterine growth Retardation; sIUGR), or in fetal haemoglobin (Twin Anaemia Polycythaemia Sequence; TAPS). There is a very wide range of ischaemic and haemorrhagic injury in a focal as well as a global distribution. Acute twin twin transfusion may account for intraventricular haemorrhage in recipients and periventricular leukomalacia in donors but there are additional risk factors for focal embolism and cerebrovascular disease. The recipient has circulatory overload, with effects on systemic and pulmonary circulations which probably lead to systemic and pulmonary hypertension and even right ventricular outflow tract obstruction as well as the polycythaemia which is a risk factor for thrombosis and vasculopathy. The donor is hypovolaemic and has a reticulocytosis in response to the anaemia while maternal hypertension and diabetes may influence stroke risk. Understanding of the mechanisms, including the role of vasculopathy, in well studied conditions such as alloimmune thrombocytopaenia and monochorionic diamniotic twinning may lead to reduction of the burden of antenatally sustained cerebral palsy.     

头皮糠疹与巯氧吡啶锌

头皮糠疹是常见病是多发病,临床表现为头皮红斑和脱屑,提示皮损部位表皮结构和功能异常,头皮角质层代谢紊乱,最近对头皮糠疹病因和病理的研究证实马拉色菌,皮脂分泌和个体敏感性是形成上述皮损的3个关键因素,硫氧吡啶锌（PTZ或ZPT）可以有效地杀灭马拉色菌,PTZ的颗粒大小和形状对其在头皮的生物利用度有明显的影响。此外,PTZ的抗菌效果有赖于其分子结构的完整性,在外用制剂中加入附加的游离锌,可以有效防止PTZ解离,从而提高其疗效。     

Diagnostic sensitivity of serum cystatin for impaired glomerular filtration rate

Recently, the reciprocal of cystatin C (Cys-C), a non-glycosylated 13-kilodalton protein that is produced by all investigated nucleated cells, was found to correlate closely with glomerular filtration rate (GFR). In order to determine the diagnostic validity in children for the detection of impaired GFR, venous blood samples from 381 children (aged 1.7–18 years) with various renal pathology referred for ⁵¹Cr-EDTA clearance investigations were obtained for measurement of Cys-C as well as β₂-microglobulin (β2-MG) and serum creatinine. Two hundred and sixteen children with clearance values >90 ml/min per 1.73 m² constituted a control group, with a normal GFR. In the control group, Cys-C values were normally distributed with a mean of 0.94±0.27 mg/l and an upper reference limit (97.5th percentile) of 1.47 mg/l. In all children, there was a positive correlation between ⁵¹Cr-EDTA clearance and the reciprocal of Cys-C (r=0.64, P<0.0001), β₂-MG (r=0.59, P<0.0001), creatinine (r=0.55, P<0.0001), and the height/creatinine ratio (r=0.73, P<0.0001). Receiver-operating characteristics analysis showed that there were no significant differences between these three parameters for discriminating between patients with normal and reduced GFR, although there was a tendency towards the best diagnostic sensitivity of the GFR estimate according to the Schwartz formula. We conclude that for the detection of mildly impaired GFR, a full clearance study cannot be replaced by measurement of serum Cys-C or β2-MG concentrations. Received: 15 June 1998 / Revised: 22 September 1998 / Accepted: 23 September 1998     

Two novel mutations of the gene for Kir 1.1 (ROMK) in neonatal Bartter syndrome

Bartter syndrome, an autosomal recessive renal tubular disorder, is associated with hypokalemic metabolic alkalosis with high renin and aldosterone plasma concentrations with low or normal blood pressure and renal salt loss. Two genes, the gene encoding the furosemide-sensitive apical Na-K-2Cl cotransporter (NKCC2) and the gene encoding the luminal inwardly-rectifying potassium channel K_ir 1.1 (ROMK), have been reported to cause the neonatal subtype of Bartter syndrome. In a patient with neonatal Bartter syndrome, we report two novel mutations resulting in amino acid exchanges Ala156Val and Leu220Phe in the gene for K_ir 1.1 that have been identified by single-strand conformation polymorphism analysis and subsequent direct sequencing. Both mutations occur in functional relevant domains of the channel protein and are therefore highly suggestive of altering channel properties. Received October 29, 1997; accepted November 6, 1997