Excimer laser angioplasty versus balloon angioplasty in functional and total coronary occlusions

Registries of excimer laser coronary angioplasty have reported good results in the treatment of complex coronary artery disease, including total or subtotal coronary occlusions. One hundred three patients (103 lesions) with a functional or total coronary occlusion were included in a randomized trial (Amsterdam-Rotterdam [AMRO] trial, total of 308 patients), 49 patients were allocated to laser angioplasty and 54 patients to balloon angioplasty. The primary clinical end points were death, myocardial infarction, coronary bypass surgery, or repeated coronary angioplasty of the randomized segment during a 6-month follow-up period. The primary angiographic end point was the minimal lumen diameter at follow-up in relation to the baseline value (net gain), as determined by an automated contour-detection algorithm. Laser angioplasty was followed by balloon angioplasty in all procedures. The angiographic success rate was 65% in patients treated with excimer laser-assisted balloon angioplasty compared with 61% in patients treated with balloon angioplasty alone. No deaths occurred. There were no significant differences between the laser angioplasty group and the balloon angioplasty group in the incidence of myocardial infarctions (1 patient vs 3, respectively, p = 0.36), coronary bypass surgery (4 patients vs 2, respectively, p = 0.34), repeat angioplasty (10 patients vs 8, respectively, p = 0.46) or primary clinical end point (15 patients vs 12, respectively, p = 0.34). The net gain in minimal lumen diameter and restenosis rate (>50% diameter stenosis at follow-up) were 0.81 +/- 0.74 mm and 66.7%, respectively, in patients treated with laser angioplasty compared with 1.04 +/- 0.68 mm and 48.5%, respectively, in patients treated with balloon angioplasty (p = 0.59 and p = 0.15, respectively). Excimer laser-assisted balloon angioplasty demonstrated no benefit over balloon angioplasty with respect to initial and long-term clinical and angiographic outcome in the treatment of patients with functional or total coronary occlusions of >10 mm in length.     

The synapse-associated protein rapsyn regulates tyrosine phosphorylation of proteins colocalized at nicotinic acetylcholine receptor clusters

Protein tyrosine phosphorylation has been suggested to play an important role in the clustering of the nicotinic acetylcholine receptor (AChR) at the developing neuromuscular junction. Recent studies have shown that the 43-kDa synapse-associated protein rapsyn induces clustering of the AChR in heterologous expression systems. In this study we examined whether tyrosine phosphorylation is involved in this rapsyn-induced AChR clustering. Rapsyn-induced AChR clusters in fibroblasts contain phosphotyrosine, as detected using immunofluorescent labeling with anti-phosphotyrosine antibodies. No anti-phosphotyrosine staining of rapsyn clusters is seen in the absence of AChR expression, indicating that the AChR is required for the appearance of phosphotyrosine at clusters. In addition, coexpression of rapsyn with the AChR induces the tyrosine phosphorylation of the beta amd delta subunits of the AChR. Surprisingly, mutation of the tyrosine phosphorylation sites in the AChR did not inhibit rapsyn-induced clustering of the AChR and clusters of the mutant AChRs still contained high levels of phosphotyrosine. Experiments with single AChR subunits demonstrate that the alpha subunit of the AChR appears to be necessary and sufficient for codistribution of phosphotyrosine with rapsyn-induced clusters of AChR subunits. Finally, transfection of cells with rapsyn activates cellular protein tyrosine kinase activity, resulting in the tyrosine phosphorylation of several membrane-associated proteins. These results suggest that rapsyn may therefore regulate clustering at least in part by regulating the tyrosine phosphorylation of cellular proteins.     

Spectroelectrochemical characterization of the metal centers in carbon monoxide dehydrogenase (CODH) and nickel-deficient CODH from Rhodospirillum rubrum

Carbon-monoxide dehydrogenase (CODH) from Rhodospirillum rubrum contains two metal centers: a Ni-X-[Fe4S4]2+/1+ cluster (C-center) that serves as the COoxidation site and a standard [Fe4S4]2+/1+ cluster (B-center) that mediates electron flow from the C-center to external electron acceptors. Four states of the C-center were previously identified in electron paramagnetic resonance (EPR) and M?ssbauer studies. In this report, EPR-redox titrations demonstrate that the fully oxidized, diamagnetic form of the C-center (Cox) undergoes a one-electron reduction to the Cred1 state (gav = 1.87) with a midpoint potential of -110 mV. The reduction of Cox to Cred1 is shown to coincide with the reduction of an [Fe4S4]2+/1+ cluster in redox-titration experiments monitored by UV-visible spectroscopy. Nickel-deficient CODH, which is devoid of nickel yet contains both [Fe4S4]2+/1+ clusters, does not exhibit EPR-active states or reduced Fe4S4 clusters at potentials more positive than -350 mV.     

Song learning and vocal tradition in Nuttall's white-crowned sparrows

We investigated song sharing and dispersion of song types in the wild in a colour-marked population of the non-migratory Nuttall's white-crowned sparrow, Zonotrichia leucophrys nuttalli. The songs of fathers, their male progeny (sons), and the neighbours of the sons at recruitment sites were analysed spectrographically and compared qualitatively and quantitatively. To determine whether a son's song more closely matched that of his father or a neighbour at the site settled, we subjected frequency and temporal characteristics of songs within each father-son-neighbour triad to multivariate cluster analysis. The songs of 14 of 16 sons clustered with their neighbours' rather than their fathers' songs, confirming that song matching of neighbours is an integral component of territory settlement by juveniles. Principal components analysis of frequency and temporal measurements of song within a dialectal area show that songs group into neighbourhoods and are non-randomly distributed. Multivariate analysis suggests that sons may entrain on frequency and temporal characteristics of a neighbour's song without matching phrases or complex syllables. Implications for models of instructive versus selective learning are discussed. The timing of closure of the sensitive phase, the length of the silent interval between the sensory phase and plastic song stage, and the time to song crystallization remain open questions in song ontogeny. Copyright 1998 The Association for the Study of Animal Behaviour. Copyright 1998 The Association for the Study of Animal Behaviour.     

Neutralization of human immunodeficiency virus type 1 by antibody to gp120 is determined primarily by occupancy of sites on the virion irrespective of epitope specificity

We investigated the relative importance of binding site occupancy and epitope specificity in antibody neutralization of human immunodeficiency virus (HIV) type 1 (HIV-1). The neutralization of a T-cell-line-adapted HIV-1 isolate (MN) was analyzed with a number of monovalent recombinant Fab fragments (Fabs) and monoclonal antibodies with a range of specificities covering all confirmed gp120-specific neutralization epitopes. Binding of Fabs to recombinant monomeric gp120 was determined by surface plasmon resonance, and binding of Fabs and whole antibodies to functional oligomeric gp120 was determined by indirect immunofluorescence and flow cytometry on HIV-infected cells. An excellent correlation between neutralization and oligomeric gp120 binding was observed, and a lack of correlation with monomeric gp120 binding was confirmed. A similar degree of correlation was observed between oligomeric gp120 binding and neutralization with a T-cell-line-adapted HIV-1 molecular clone (Hx10). The ratios of oligomer binding/neutralization titer fell, in general, within a relatively narrow range for antibodies to different neutralization epitopes. These results suggest that the occupancy of binding sites on HIV-1 virions is the major factor in determining neutralization, irrespective of epitope specificity. Models to account for these observations are proposed.     

The contribution of classical (beta1/2-) and atypical beta-adrenoceptors to the stimulation of human white adipocyte lipolysis and right atrial appendage contraction by novel beta3-adrenoceptor agonists of differing selectivities

The role of beta3- and other putative atypical beta-adrenoceptors in human white adipocytes and right atrial appendage has been investigated using CGP 12177 and novel phenylethanolamine and aryloxypropanolamine beta3-adrenoceptor (beta3AR) agonists with varying intrinsic activities and selectivities for human cloned betaAR subtypes. The ability to demonstrate beta1/2AR antagonist-insensitive (beta3 or other atypical betaAR-mediated) responses to CGP 12177 was critically dependent on the albumin batch used to prepare and incubate the adipocytes. Four aryloxypropanolamine selective beta3AR agonists (SB-226552, SB-229432, SB-236923, SB-246982) consistently elicited beta1/2AR antagonist-insensitive lipolysis. However, a phenylethanolamine (SB-220646) that was a selective full beta3AR agonist elicited full lipolytic and inotropic responses that were sensitive to beta1/2AR antagonism, despite it having very low efficacies at cloned beta1- and beta2ARs. A component of the response to another phenylethanolamine selective beta3AR agonist (SB-215691) was insensitive to beta1/2AR antagonism in some experiments. Because no [corrected] novel aryloxypropanolamine had a beta1/2AR antagonist-insensitive inotropic effect, these results establish more firmly that beta3ARs mediate lipolysis in human white adipocytes, and suggest that putative 'beta4ARs' mediate inotropic responses to CGP 12177. The results also illustrate the difficulty of predicting from studies on cloned betaARs which betaARs will mediate responses to agonists in tissues that have a high number of beta1- and beta2ARs or a low number of beta3ARs.     

Six-month clinical and angiographic outcome of the new, less shortening Wallstent in native coronary arteries

BACKGROUND: The new, less shortening, self-expanding Wallstent is characterized by longitudinal flexibility, a protective membrane, a low profile, and a customized range of diameters (3.5 to 6.0 mm). The recent modification of the braiding angle of the Wallstent has resulted in a new device with less shortening on expansion and a concomitant reduction in radial force. We hypothesized that the enforced mechanical remodeling produced by the selection of an oversized Wallstent might result in improved accommodation of subsequent reactive intimal hyperplasia and prevention of chronic recoil of the vessel. METHODS AND RESULTS: To prove this hypothesis, we recently implanted 44 new, less shortening Wallstents in 35 native coronary arteries in 35 patients with acute or threatened closure after balloon angioplasty, according to a strategy of oversizing of Wallstent diameter and complete coverage of the lesion length. The initial and 6-month follow-up angiograms were analyzed with a computer-based quantitative coronary angiography (QCA) system. Acute gain (minimal luminal diameter [MLD] post minus MLD pre) and late loss (MLD post minus MLD at follow-up) were examined. Stent deployment was successful in 44 of 44 attempts (100%). Nominal stent diameter used was 1.40 mm larger than the maximal vessel diameter. One patient (3%) with a dilated but unstented lesion proximal to the stented segment sustained a subacute occlusion on day 1 associated with myocardial infarction. Event-free survival at 30 days after stent implantation was 97% (34 of 35 patients). Of the 34 patients eligible for 6-month angiographic follow-up, 3 who were asymptomatic declined repeat angiography. MLD (and percent diameter stenosis [% DS]) changed from 0.83 +/- 0.50 mm (72%) pre through 3.06 +/- 0.48 mm (15%) post to 2.27 +/- 0.74 mm (28%) at follow-up. Acute gain was 2.23 +/- 0.63 mm, and late loss was 0.78 +/- 0.61 mm. Angiographic restenosis ( > 50% DS) was observed in 5 of 31 patients (16%) at 6 months, all of whom underwent repeat angioplasty. Thus, the overall event-free survival at 6-month follow-up was 83% (29 of 35 patients). CONCLUSIONS: The oversized Wallstent implantation with complete coverage of the lesion length conveyed a favorable 6-month clinical and angiographic outcome. The large acute gain obtained by the Wallstent afforded greater accommodation of the subsequent late loss. The enforced mechanical remodeling by oversized new Wallstents may result in prevention of acute and chronic recoil of the vessel wall and subsequently a lower restenosis rate at follow-up.     

Initial cervical exploration for parathyroidectomy is not benefited by preoperative localization studies

Published data is controversial as to the ability of preoperative localization studies (PLS) to enhance the outcome of initial cervical exploration in patients with primary hyperparathyroidism (PHPT). One surgeon's experience was reviewed to compare surgical success, operative time, and morbidity of initial cervical exploration for PHPT in patients who had undergone PLS versus those who had not. From August 1991 to September 1997, 95 patients who had not undergone prior central cervical exploration presented for surgical management of PHPT. Sixty-seven patients underwent initial cervical exploration without any PLS having been performed (Group A). Twenty-eight patients underwent PLS, either alone or in combination, before surgical intervention (Group B). Analysis of intergroup variability was conducted upon the data available using a two-tailed t test for independent samples. In addition, the sensitivities and positive predictive values of the PLS were calculated using study reports and operative and histologic findings. There was no statistically significant difference in surgical success between those patients who had PLS and those that did not undergo PLS. Sixty-four of 67 patients (95.5%) not having PLS were cured with initial surgery, while 27 of 28 patients (96.4%) who had PLS were surgically cured. Mean postoperative calcium and intact parathormone levels were similar between the two groups, and the mean operative time did not differ. Permanent hypocalcemia occurred in one patient, and five patients had transient hoarseness. Thirty-six total PLS were obtained at an average cost of $752.68/patient, and seven patients underwent multiple tests. Overall, sestamibi scan had the highest positive predictive value (81%). For adenomatous disease alone, sestamibi scan was the most sensitive (83%). Our study shows that for matched groups limited to age, sex, and clinical diagnosis, the use of PLS did not shorten operative time, decrease complication frequency, nor alter the success of the operation as measured by postoperative calcium and parathormone levels. Therefore, routine use of preoperative localization studies before initial cervical exploration for PHPT cannot be recommended.