Multilocus linkage identifies two new loci for a mendelian form of stroke, cerebral cavernous malformation, at 7p15-13 and 3q25.2-27

Cerebral cavernous malformation (CCM) is a Mendelian model of stroke, characterized by focal abnormalities in small intracranial blood vessels leading to hemorrhage and consequent strokes and/or seizures. A significant fraction of cases is inherited as an autosomal dominant trait with incomplete penetrance. Among Hispanic Americans, virtually all CCM is attributable to a founder mutation localized to 7q ( CCM1 ). Recent analysis of non-Hispanic Caucasian kindreds, however, has excluded linkage to 7q in some, indicating at least one additional CCM locus. We now report analysis of linkage in 20 non-Hispanic Caucasian kindreds with familial CCM. In addition to linkage to CCM1, analysis of linkage demonstrates linkage to two new loci, CCM2 at 7p13-15 and CCM3 at 3q25.2-27. Multilocus analysis yields a maximum lod score of 14.11, with 40% of kindreds linked to CCM1, 20% linked to CCM2 and 40% linked to CCM3, with highly significant evidence for linkage to three loci (linkage to three loci supported with an odds ratio of 2.6 x 10(5):1 over linkage to two loci and 1.6 x 10(9):1 over linkage to one locus). Multipoint analysis among families with high posterior probabilities of linkage to each locus refines the locations of CCM2 and CCM3 to approximately 22 cM intervals. Linkage to these three loci can account for inheritance of CCM in all kindreds studied. Significant locus- specific differences in penetrance are identified. These findings have implications for genetic testing of this disorder and represent an important step toward identification of the molecular basis of this disease.      

Conservative management of azoospermia following steroid abuse

As well as athletes and competitive body builders, recreational body builders attending gymnasia are known to abuse anabolic steroids, using doses from 10- to 40-fold above physiological levels. Androgenic steroids induce hypogonadotrophic hypogonadism with associated azoospermia, leading to infertility. Little literature exists on the treatment of steroid-induced azoospermia following the cessation of abuse. We present four cases of steroid-induced azoospermia, its conservative management and eventual return of normal semen density.      

A comparison of pulmonary and femoral artery thermodilution cardiac indices in paediatric intensive care patients

We have assessed the agreement between pulmonary artery and femoral artery (COLD) thermodilution measurements of the cardiac index (C1) in a group of paediatric intensive care patients. The COLD method gave consistently higher cardiac index values than the pulmonary artery catheter (PAC); however, the difference was small, with a mean value of 0.191/min⁻¹ m⁻² or 4.4% of the mean cardiac index. This difference is not clinically important and suggests that, under these circumstances. the COLD system provides an acceptable alternative to the pulmonary artery catheter for measurement of the cardiac index at the bedside.     

Perioperative haemodynamic effects of an intravenous infusion of calcium chloride in children following cardiac surgery

Murdoch IA, Qureshi SA, Huggon IC. Perioperative haemodynamic effects of an intravenous infusion of calcium chloride in children following cardiac surgery. Acta Pzdiatr 1994;83:658–61. Stockholm. ISSN 0803–5253
Twelve children received an infusion of 10% calcium chloride 0.1 ml/kg to a maximum dose of 5 ml, infused over 5 min, following open heart surgery. Blood ionized calcium, systemic arterial pH, cardiac index, mean systemic arterial blood pressure and systemic vascular resistance index were measured at baseline and repeated 20 and 40 min following completion of the infusion. There was considerable overlap, with no significant differences in the response to the calcium chloride infusion between children with ionized hypocalcaemia (< 1.1 mmol/l) and those with ionized normocalcaemia when its effect on percentage change in either the haemodynamic or biochemical measurements was assessed ( p>0.2 for all measurements; Mann-Whitney). For this reason they were treated as a single group. Significant changes from baseline were noted in mean systemic arterial pressure (p 10.02), cardiac index (p<0.01) and systemic vascular resistance index (p<0.01) after completion of the calcium chloride infusion when analysed using Friedman's two-way analysis of variance. A significant increase in mean systemic arterial blood pressure occurs after an infusion of 10% calcium chloride as a direct result of an increase in the systemic vascular resistance index with a concomitant decrease in cardiac index.     

Positive and negative modulation of group I metabotropic glutamate receptors

A discriminating pharmacophore model for noncompetitive metabotropic glutamate receptor antagonists of subtype 1 (mGluR1) was developed that facilitated the discovery of moderately active mGluR1 antagonists. One scaffold was selected for the design of several focused libraries where different substitution patterns were introduced. This approach facilitated the discovery of potent mGluR1 antagonists, as well as positive and negative mGluR5 modulators, because both receptor subtypes share similar binding pockets. For mGluR1 antagonists, a homology model of the mGlu1 receptor was established, and a putative binding mode within the receptor's transmembrane domain was visualized.     

小儿严重外伤性硬脑膜静脉窦损伤19例

目的探讨小儿严重硬脑膜静脉窦损伤的治疗方法。方法回顾性分析19例小儿严重硬脑膜外伤性静脉窦损伤的诊治经过。19例中,采取上矢状窦结扎4例,上矢状窦修补14例,人造血管静脉窦重建1例。在处理静脉窦损伤的同时行颅内血肿清除及颅骨凹陷骨折复位术,其中7例开放性损伤患儿均行颅骨片一期植入术。结果全组痊愈14例(73.6%),肢体瘫痪2例(10.5%),死亡3例(15.7%)。术中平均失血量500 ml(200～4000 ml),其中8例出现失血性休克。3例死亡患儿均因术中严重失血导致不可逆性休克而死亡。结论小儿严重硬脑膜静脉窦损伤伤情重,处理困难,术中死亡率高。术前应根据颅骨骨折类型、部位及程度对静脉窦损伤作出诊断,充分准备,快速控制大出血,果断采取不同的止血及修补措施,以达到止血及恢复静脉窦通畅的目的。