Defects in mismatch repair occur after APC mutations in the pathogenesis of sporadic colorectal tumours

The roles of the intrinsic mutation rate and genomic instability in tumorigenesis are currently controversial. In most colorectal tumours, it is generally supposed that the first mutations occur at the adenomatous polyposis coli (APC) locus; APC mutations are thought to provide cells with a selective advantage but have no known effect on the mutation rate. It has also been suggested that genomic instability is the initiating event in colorectal tumorigenesis and, if this is true, mutations of DNA mismatch repair (MMR) genes (or at similar loci) are the most likely candidates. If defective MMR precedes APC mutations, the APC mutations of colon tumours with defective MMR and hence replication errors (RER+) should differ from those of RER- tumours, in at least three specific ways: (1) a higher frequency of allele loss at APC in RER- tumours; (2) more frameshift than nonsense mutations in RER+ tumours; and (3) APC mutations in simple repeat sequences [(N)_n, (N₁N₂)_n, or (N₁N₂N₃)_n] in RER+ tumours. We found no evidence that sporadic RER+ and RER- colon cancers (including cell lines) differ in any of these three ways. Although it remains possible that MMR is abnormal in tumours from HNPCC families before APC mutations occur, it is likely that in sporadic colon tumours, APC mutations, rather than genomic instability, are the initiating events in tumorigenesis. Hum Mutat 11:114–120, 1998. © 1998 Wiley-Liss, Inc.     

颅内蛛网膜囊肿34例

1　临床资料1.1　一般资料　 1986 / 1997收治颅内蛛网膜囊肿 34(男 2 8,女 6 )例 .年龄 3～ 6 8岁 ,其中 16岁以下 17例 .有头部外伤史者 15例 ,无明显诱因者 19例 .病程 :2 m o～ 14a.头部外伤至发病时间 :7d～ 2 a. 34例中幕上 30例 ,幕下 4例 ,其中侧裂池 15例 .1.2　临床症状　表现头疼、头昏或伴呕吐、视力下降、视乳头水肿等颅内压增高的症状 18例 ,癫痫发作 7例 ,偏瘫 6例 ,行走不稳 2例 ,失语 1例 .1.3　辅助检查　本组 2 8例作 CT检查 ,6例行 MRI检查证实 .头颅 CT扫描特征 :脑实质外有一边界清楚的低密度病灶 ,CT值与脑脊液…     

Modification of GABA-mediated inhibition by various injectable anesthetics.

Increasing doses of the injectable anesthetics etomidate, Saffan, thiopental, ketamine, and xylazine and the vehicles saline and propylene glycol were administered to urethane-anesthetized rats. Their effects in vivo on perforant pathway-evoked field excitatory post-synaptic potentials and population spikes in the hippocampal dentate gyrus were determined. The primary purpose was to ascertain whether these compounds affect hippocampal excitability in a manner consistent with their proposed mechanisms of action. Compared with their respective vehicles, thiopental, etomidate, and xylazine reduced the amplitude of population spikes to single perforant pathway stimulation by 20-30% at the highest doses tested. Xylazine also increased the latency to onset of the population spike. No other effects were observed. Using paired pulse paradigms, it was determined that etomidate produced a dramatic, prolonged reduction in granule cell excitability at interpulse intervals of 10-100 ms. The magnitude of the effect was dose related and was reversible with the discontinuance of administration of the drug. Similar changes occurred with Saffan (althesin) and thiopental. Ketamine produced a small but significant depression in granule cell excitability during intervals of 10-200 ms. Xylazine had no effect. These data corroborate the importance of a prolongation of gamma-aminobutyric acid A-mediated inhibition to the mechanism of actions of etomidate, thiopental, and Saffan at relevant exposure concentrations in vivo.     

Three-compartment wrist arthrography: use of a low-iodine-concentration contrast agent to decrease study time

To decrease examination time, the authors used a contrast agent with a low iodine concentration for three-compartment (radiocarpal joint, distal radioulnar joint, midcarpal compartment) wrist arthrography. The material was used in 24 patients. Many patients demonstrated dissipation of contrast material in the radiocarpal joint by 30 minutes after injection. By 45 minutes, all patients demonstrated sufficient dissipation to permit the second injection. The technique produces diagnostic images and reduces the time required for the study.     

Tricyclic antidepressant overdose: emergency department findings as predictors of clinical course

There is controversy regarding the appropriate utilization of health care resources in the management of tricyclic antidepressant overdosage. Antidepressant overdose patients presenting to the emergency department (ED) are routinely admitted to intensive care units, but only a small proportion develop cardiac arrhythmias or other complications requiring such an environment. The authors reviewed the findings in 165 patients presenting to an ED with antidepressant overdose. They found that major manifestations of toxicity on ED evaluation (altered mental status, seizures, arrhythmias, and conduction defects) were commonly associated with a complicated hospital course. Patients with the isolated findings of sinus tachycardia or QTc prolongation had no complications. No patient experienced a serious toxic event without major evidence of toxicity on ED evaluation and continued evidence of toxicity during the hospital course. These data support the concept that proper ED evaluation can identify a large body of patients with trivial ingestions who may not require hospital observation.