人体液中喷布洛尔及其代谢物的GC/MS分析

用气相色谱一质谱联用(GC-MSD)系统分析方法检出了人尿中喷布洛尔的6个羟化代谢物,用Scp-Pak柱提取的方法检出了人血浆中的原型药物。并从分子结构上对此药物的代谢途径进行了研究。尿中提取和血中提取的回收率分别为90.83.%和85.88%,Gc-MSD的检测限为5pg。本方法适用于运动员兴奋剂的系统检查。     

Acute epidural hematoma: an analysis of factors influencing the outcome of patients undergoing surgery in coma

Mortality due to epidural hematoma is virtually restricted to patients who undergo surgery for that condition while in coma. The authors have analyzed the factors influencing the outcome of 64 patients who underwent epidural hematoma evacuation while in coma. These patients represented 41% of the 156 patients operated on for epidural hematoma at their centers after the introduction of computerized tomography (CT). Eighteen patients (28.1%) died, two (3.1%) became severely disabled, and 44 (68.8%) made a functional recovery. The mortality rate for the entire series was 12%, significantly lower than the 30% rate observed when only angiographic studies were available. A significant correlation was found between the final result and the mechanism of injury, the interval between trauma and surgery, the motor score at operation, the hematoma CT density (homogeneous vs. heterogeneous), and the hematoma volume. The patient's age, the course of consciousness before operation (whether there was a lucid interval), and the clot location did not correlate with the final outcome. The mortality rate was significantly higher in patients operated on within 6 hours or between 6 and 12 hours after injury than in those undergoing surgery 12 to 48 hours after injury. Compared with the patients operated on later, the patients undergoing surgery in the early period were, on the average, older and had more rapidly developing symptoms, more pupillary changes, lower motor scores at surgery, larger hematomas, a higher incidence of mixed CT density clots, more severe associated intracranial lesions, and higher postoperative intracranial pressure (ICP). The mechanism of trauma seems to influence the course of consciousness before and after surgery. Passengers injured in traffic accidents had a lower incidence of a lucid interval and longer postoperative coma than patients with low-speed trauma, suggesting more frequent association of diffuse white matter-shearing injury. The duration of postoperative coma correlated with the morbidity rate in survivors. Forty-eight patients (75%) had one or more associated intracranial lesions, and 70% of these required treatment for elevation of ICP after hematoma evacuation. An ICP of over 35 mm Hg strongly correlated with poor outcome; administration of high-dose barbiturates was the only effective means for lowering ICP in nine of 15 patients who developed severe intracranial hypertension after surgery. This study attempts to identify patients at greater risk for presenting postoperative complications and to define a strategy for control CT scanning and ICP monitoring.     

Extradural hematoma: analysis of factors influencing the courses of 161 patients

The clinical and computed tomographic (CT) findings in a series of 161 consecutive patients operated upon for postraumatic extradural hematoma are analyzed. Thirteen (8%) patients had delayed epidural hematoma formation. The overall mortality for the series was 12%, significantly lower than that observed during the prior "angiographic" period at the same unit (30%). Because all but 1 of the deaths occurred among the 66 patients unconscious at the time of operation (27% mortality in this subgroup), the authors sought differential factors between comatose and noncomatose patients at operation. There were no significant differences between these groups in age, sex, mechanism of injury, preoperative course of consciousness (lucid interval or not), or epidural hematoma location and shape. In contrast, significant differences were seen between the two subgroups in trauma-to-operation interval, hematoma volume, CT hematoma density (mixed low-high CT density vs. homogeneous hyperdensity), midline displacement, severity of associated intracranial lesions, and postoperative intracranial pressure (ICP). Patients comatose at operation usually evidenced a more rapid clinical deterioration (a shorter trauma-to-operation interval) and tended to have a large hematoma volume, a higher incidence of mixed CT density clot (hyperacute bleeding), more marked shift of midline structures, more severe associated lesions, and higher postoperative ICP levels.     

Subarachnoid haemorrhage of unknown aetiology

Summary The authors review the literature on subarachnoid haemorrhage of unknown aetiology (SAHUE) and analyze a personal series of 212 patients diagnosed as SAHUE. These patients represent 30% of all cases of primary SAH admitted over a 14.5 year period.The age, sex, antecedents and initial clinical presentation of patients with SAHUE were indistinguishable from those of patients with subarachnoid haemorrhage due to ruptured aneurysm (SAHRA). However, the present series of SAHUE compare favourably with both a personal and a previously reported series of SAHRA insofar as clinical grade on admission (94% of patients in grades I–II of Botterell), presence of blood on CT (51%), vasospasm (5%), ischaemic deficits (3.3%), persistent hydrocephalus (3.5%), rebleeding (6%) and fatal result (3.9%) are concerned.The amount of blood on CT scan in our patients with SAHUE was associated with a significantly higher incidence of brain ischaemia and hydrocephalus but did not correlate with the Botterell grade on admission or final outcome, which were good in the majority of cases regardless of the presence or not of visible cisternal haemorrhage. The results of the present series confirm that the final prognosis of patients with primary SAH showing normal four-vessel cerebral angiography is essentially favourable.     

Androgen receptor YAC transgenic mice carrying CAG 45 alleles show trinucleotide repeat instability

X-linked spinal and bulbar muscular atrophy (SBMA) is caused by a CAG repeat expansion in the first exon of the androgen receptor (AR) gene. Disease-associated alleles (37-66 CAGs) change in length when transmitted from parents to offspring, with a significantly greater tendency to shift size when inherited paternally. As transgenic mice carrying human AR cDNAs with 45 and 66 CAG repeats do not display repeat instability, we attempted to model trinucleotide repeat instability by generating transgenic mice with yeast artificial chromosomes (YACs) carrying AR CAG repeat expansions in their genomic context. Studies of independent lines of AR YAC transgenic mice with CAG 45 alleles reveal intergenerational instability at an overall rate of approximately 10%. We also find that the 45 CAG repeat tracts are significantly more unstable with maternal transmission and as the transmitting mother ages. Of all the CAG/CTG repeat transgenic mice produced to date the AR YAC CAG 45 mice are unstable with the smallest trinucleotide repeat mutations, suggesting that the length threshold for repeat instability in the mouse may be lowered by including the appropriate flanking human DNA sequences. By sequence-tagged site content analysis and long range mapping we determined that one unstable transgenic line has integrated an approximately 70 kb segment of the AR locus due to fragmentation of the AR YAC. Identification of the cis - acting elements that permit CAG tract instability and the trans -acting factors that modulate repeat instability in the AR YAC CAG 45 mice may provide insights into the molecular basis of trinucleotide repeat instability in humans.