Progression of asymptomatic carotid stenosis: a natural history study in 1004 patients

PURPOSE: The purpose of this study was to delineate the natural history of the progression of asymptomatic carotid stenosis. METHODS: In a 10-year period, 1701 carotid arteries in 1004 patients who were asymptomatic were studied with serial duplex scans (mean follow-up period, 28 months; mean number of scans, 2.9/patient). At each visit, stenoses of the internal carotid artery (ICA) and the external carotid artery (ECA) were categorized as none (0 to 14%), mild (15% to 49%), moderate (50% to 79%), severe (80% to 99%), preocclusive, or occluded. Progression was defined as an increase in ICA stenosis to >/=50% for carotid arteries with a baseline of <50% or as an increase to a higher category of stenosis if the baseline stenosis was >/=50%. The Cox proportional hazards model was used for data analysis. RESULTS: The risk of progression of ICA stenosis increased steadily with time (annualized risk of progression, 9.3%). With multivariate modeling, the four most important variables that affected the progression (P <.02) were baseline ipsilateral ICA stenosis >/=50% (relative risk [RR], 3.34), baseline ipsilateral ECA stenosis >/=50% (RR, 1.51), baseline contralateral ICA stenosis >/=50% (RR, 1.41), and systolic pressure more than 160 mm Hg (RR, 1. 37). Ipsilateral neurologic ischemic events (stroke/transient ischemic attack) occurred in association with 14.0% of the carotid arteries that were studied. The progression of ICA stenosis correlated with these events (P <.001), but baseline ICA stenosis was not a significant predictor. CONCLUSION: In contrast to recently published studies, we found that the risk of progression of carotid stenosis is substantial and increases steadily with time. Baseline ICA stenosis was the most important predictor of the progression, but baseline ECA stenosis also was identified as an important independent predictor. Contralateral ICA stenosis and systolic hypertension were additional significant predictors. We found further that the progression of ICA stenosis correlated with ischemic neurologic events but not baseline stenosis. The data provide justification for the use of serial duplex scans to follow carotid stenosis and suggest that different follow-up intervals may be appropriate for different patient subgroups.     

弛豫SiGe外延层的UHV/CVD生长

利用自制的冷壁石英腔UHV/CVD设备,600℃条件下,通过Ge组分渐变缓冲层技术,在Si(100)衬底上成功地生长出完全弛豫、无穿透位错的Si0.83Ge0.17外延层,并在其上获得了具有张应变的Si盖帽层.另外,还在550℃下生长了同样结构的样品,发现此样品厚度明显变薄,组分渐变层的应变释放不完全,位错网稀疏而且不均匀,其上的Si0.83Ge0.17外延层具有明显的穿透位错     

Organization of neural inputs to the suprachiasmatic nucleus in the rat

The circadian timing of the suprachiasmatic nucleus (SCN) is modulated by its neural inputs. In the present study, we examine the organization of the neural inputs to the rat SCN using both retrograde and anterograde tracing methods. After Fluoro-Gold injections into the SCN, retrogradely labeled neurons are present in a number of brain areas, including the infralimbic cortex, the lateral septum, the medial preoptic area, the subfornical organ, the paraventricular thalamus, the subparaventricular zone, the ventromedial hypothalamic nucleus, the posterior hypothalamic area, the intergeniculate leaflet, the olivary pretectal nucleus, the ventral subiculum, and the median raphe nuclei. In the anterograde tracing experiments, we observe three patterns of afferent termination within the SCN that correspond to the photic/raphe, limbic/hypothalamic, and thalamic inputs. The median raphe projection to the SCN terminates densely within the ventral subdivision and sparsely within the dorsal subdivision. Similarly, areas that receive photic input, such as the retina, the intergeniculate leaflet, and the pretectal area, densely innervate the ventral SCN but provide only minor innervation of the dorsal SCN. A complementary pattern of axonal labeling, with labeled fibers concentrated in the dorsal SCN, is observed after anterograde tracer injections into the hypothalamus and into limbic areas, such as the ventral subiculum and infralimbic cortex. A third, less common pattern of labeling, exemplified by the paraventricular thalamic afferents, consists of diffuse axonal labeling throughout the SCN. Our results show that the SCN afferent connections are topographically organized. These hodological differences may reflect a functional heterogeneity within the SCN.     

Diagnostic and prognostic role of basic fibroblast growth factor in Wilms' tumor patients

Basic fibroblast growth factor (bFGF) is a potent angiogenic peptide implicated in the growth and metastasis of solid tumors. Elevated concentrations of bFGF have been found in the urine of patients with bladder, prostate, and renal tumors. Furthermore, urinary bFGF levels have been shown to correlate with extent of disease. In order to test the utility of urinary bFGF as a Wilms' tumor marker, we measured bFGF levels in preoperative and postoperative urine samples from 97 patients with Wilms' tumor. Preoperative urine samples (n = 97), early postoperative samples obtained from 1 to 3 weeks after surgery (n = 43), and late postoperative samples obtained from 1 to 6 months after surgery (n = 66) were collected from Wilms' tumor patients at 30 institutions between 1989 and 1993. Urine samples from age-matched controls (n = 17) were also obtained. The bFGF levels were determined in duplicate by a competitive sandwich ELISA capable of measuring bFGF at the pg/ml level. Samples were normalized for creatinine content. Urinary bFGF was elevated in 42% of preoperative samples when compared to controls (>90th percentile of normal). Patients with stage III, IV, and V disease had significantly higher preoperative levels of urinary bFGF when compared to patients with stage I and II disease (P < 0.01). Patients with relapse or persistent disease had significantly elevated late postoperative bFGF levels when compared to disease-free patients and controls (P < 0.05). Thus, in patients with Wilms' tumor, elevated preoperative urinary bFGF levels raise the suspicion of aggressive disease while elevated postoperative levels may indicate recurrence or persistence of disease. These data suggest that bFGF is a biological marker for Wilms' tumor and may have a role in the evaluation of patients with this disease.     

The significance of electrocardiography in locating original sites of ventricular tachycardia

The sites of origin of ventricular tachycardia (VT) in 12 patients were located by ECG during the episode and further confirmed by catheter mapping. The results showed that there were 14 sites of origin of VT in the 12 patients from ECG in which 1 site was incompletely mapped by catheter and 12 of the other 13 original sites were confirmed by the catheter endocardial or epicardial mapping. Of the 12 original sites of VT, the locating of 11 ones were completely consistent with those from ECG, which was 84.6% of the 13 original sites. Moreover, 8 of the 12 patients had been successfully treated by catheter direct or radiofrequency current ablation and 1 of the 12 by successful surgical operation. Thus, the original sites of VT located by ECG was reliable and could shorten the time of catheter mapping during non-pharmacological therapy of VT.     

Role of the carboxyl-terminal lectin domain in self-association of galectin-3

Galectin-3 is a member of a large family of beta-galactoside-binding animal lectins and is composed of a carboxyl-terminal lectin domain connected to an amino-terminal nonlectin part. Previous experimental results suggest that, when bound to multivalent glycoconjugates, galectin-3 self-associates through intermolecular interactions involving the amino-terminal domain. In this study, we obtained evidence suggesting that the protein self-associates in the absence of its saccharide ligands, in a manner that is dependent on the carboxyl-terminal domain. This mode of self-association is inhibitable by the lectin's saccharide ligands. Specifically, recombinant human galectin-3 was found to bind to galectin-3C (the carboxyl-terminal domain fragment) conjugated to Sepharose 4B and the binding was inhibitable by lactose. In addition, biotinylated galectin-3 bound to galectin-3 immobilized on plastic surfaces and the binding could also be inhibited by various saccharide ligands of the lectin. A mutant with a tryptophan to leucine replacement in the carboxyl-terminal domain, which exhibited diminished carbohydrate-binding activity, did not bind to galectin-3C-Sepharose 4B. Furthermore, galectin-3C formed covalent homodimers when it was treated with a chemical cross-linker and the dimer formation was completely inhibited by lactose. Therefore, galectin-3 can self-associate through intermolecular interactions involving both the amino- and the carboxyl-terminal domains and the relative contribution of each depends on whether the lectin is bound to its saccharide ligands.     

Aspartate substitutions establish the concerted action of P-region glutamates in repeats I and III in forming the protonation site of L-type Ca2+ channels

Hydrogen ions reduce ion flux through voltage-gated Ca2+ channels by binding to a single protonation site with an unusually high pKa. Recent evidence localizes the protonation site to the same locus that supports high affinity Ca2+ binding and selectivity, a set of four conserved glutamate residues near the external mouth of the pore. Remaining controversy concerns the question of whether the protonation site arises from a single glutamate, Glu-1086 (EIII), or a combination of Glu-1086 and Glu-334 (EI) working in concert. We tested these hypotheses with individual Glu --> Asp substitutions. The Glu --> Asp replacements in repeats I and III stood out in two ways. First, in both EID and EIIID, protonation was destabilized relative to wild type, whereas it was unchanged in EIID and stabilized in EIVD. The changes in affinity were entirely due to alterations in H+ off-rate. Second, the ratio of protonated conductance to deprotonated conductance was significantly closer to unity for EID and EIIID than for wild-type channels or other Asp mutants. Both results support the idea that EI and EIII act together to stabilize a single titratable H+ ion and behave nearly symmetrically in influencing pore conductance. Neutralization of EIII by alanine replacement clearly failed to abolish susceptibility to protonation, indicating that no single glutamate was absolutely required. Taken together, all the evidence supports a model in which multiple carboxylates work in concert to form a single high affinity protonation site.