Assessment of percutaneous transluminal coronary angioplasty by quantitative coronary angiography: Diameter versus densitometric area measurements

Cineangiograms of 138 patients who underwent percutaneous transluminal coronary angioplasty (PTCA) were analyzed with a computer-based coronary angiography analysis system. The results before and after dilatation are presented. In a first study group (120 patients), the severity of the obstructive lesions derived from the automatically detected contours was evaluated in absolute terms and in percent-diameter reduction. In a second group of patients, 18 coronary lesions were selected for their extreme severity and symmetric aspect before angioplasty as assessed from multiple views. In the second group, the densHometric percent-area stenosis was used to assess the changes in cross-sectional area after PTCA and was compared with the circular percent-area stenosis computed from the diameter measurements. Before PTCA, a good agreement exists between the densitometric percent-area stenosis and the circular percent-area stenosis. After PTCA, important discrepancies between these 2 types of measurements are observed. It is suggested that these discrepancies in results after PTCA can be accounted for by asymmetric morphologic changes in luminal cross section, which cannot be assessed accurately from diameter measurements in a single-plane view.     

Concerns on carotid stenting in octogenarians: reply

Barracchini and Ballotta¹ point out some important issues concerningour registry data on carotid artery stenting (CAS) as well ason CAS in general. They mention that a distinction neither between ischemic andhaemorrhagic stroke nor between different types of     

Estrogens acting as cardiovascular agents: direct vascular actions

In vitro experiments and in vivo studies indicate that estrogens exert various beneficial effects on the vascular wall. In the present review the recent literature and the results of our own studies on this topic are summarized. By modulating the synthesis of nitric oxide, prostacyclin and endothelin and blocking calcium channels estrogens positively affect the vasotonus. Atherogenesis, which is considered an inflammatory, fibroproliferative process, may be delayed by estrogens via downregulation of inflammatory markers, such as cell adhesion molecules and chemokines. The delay is further supported by the inhibition of smooth muscle cell proliferation and downregulation of angiotensin receptor gene expression as well as by its antioxidative property. In addition, estrogens may stabilize the atherosclerotic plaque by reducing the expression of matrix metalloproteinases. The thrombogenic potency of the ruptured plaque may be reduced also by estrogens via downregulating the synthesis of plasminogen activator inhibitor-1. In addition, own clinical studies suggest that other non-endothelial derived vasoactive surrogate markers, such as serotonin and urodilatin, may be positively influenced by estrogens. Differential effects of progestin addition were observed concerning the direct estrogenic effects on the vasculature. Antagonistic progestin effects have been observed for some markers and may depend on the type of progestin and on its administration mode. Thus, the role of progestin addition remains to be elucidated in further studies.     

Intra-mammary tumor location does not influence prognosis but influences the prevalence of axillary lymph-node metastases

Background The number of axillary lymph-node metastases is not only a function of disease progression in primary breast cancer, but is also influenced by the intra-mammary location of the tumor. Nevertheless, the prognostic role of the tumor site is discussed controversially. The objective of this study was to analyze the impact of primary-tumor location on axillary lymph-node involvement, relapse, and mortality risk by univariate and multivariate analysis, in patients both with and without systemic and loco-regional treatment.Method Retrospective analysis was conducted on 2,414 patients at the I. Frauenklinik, Ludwig-Maximilians University, Munich and Berlin-Charlottenburg, who underwent R₀ resection of the primary tumor and systematic axillary lymph-node dissection (at least five lymph nodes resected) for UICC I-III-stage breast cancer. Patients with unknown tumor site, multifocal tumor spread, central tumor location, or tumor location within 15° of the border between outer and inner quadrants were excluded from the study. Median observation time was 6.7 years.Results The primary tumor site was within or between the medial quadrants of the breast in 33.6% of the patients (n=810) and in the lateral hemisphere of the breast in 66.4% (n=1,604). Tumor size, histopathological grading, and estrogen receptor status were balanced between patients with lateral and medial tumor location. Metastatic axillary lymph-node involvement was significantly associated with a lateral tumor location (P<0.0001). The mean number of axillary lymph-node metastases was increased by 29% in cases with lateral tumor location (2.2 vs 1.7, P=0.003). In a multivariate logistic regression analysis allowing for tumor location, estrogen receptor status, grading and tumor size, tumor location was confirmed as a significant risk factor (P=0.02) for axillary lymph-node involvement. Tumor location, however, did not correlate with either disease-free survival (DFS) or overall survival (OS), by univariate (DFS: P=0.41; OS: P=0.57) or by multivariate analysis (DFS: P=0.16; OS: P=0.98).Conclusion We conclude that there is no sufficient evidence to support any independent prognostic significance of intra-mammary tumor location in early breast cancer. However, medial tumor location may lead to the underestimation of axillary lymph-node involvement.     

Fade of pulmonary function during residual neuromuscular blockade

OBJECTIVES: A decrement in evoked muscle force with repetitive nerve stimulation (fade) suggests impaired neuromuscular transmission. We tested the hypothesis that fade of pulmonary function, ie, a decrease in values of FVC with the second spirometric maneuver compared to the first maneuver, occurs during impaired neuromuscular transmission. DESIGN: Prospective study. PARTICIPANTS: Six healthy male volunteers. INTERVENTIONS: A series of three consecutive spirometric maneuvers was performed every 5 min in six awake healthy volunteers before, during, and after partial paralysis evoked by rocuronium (0.01 mg/kg IV plus 2 to 8 microg/kg/min). MEASUREMENTS AND RESULTS: We measured FVC, FEV(1), forced inspiratory volume in 1 s (FIV(1)), peak expiratory flow (PEF), and peak inspiratory flow (PIF) by spirometry, and force of adductor pollicis muscle by mechanomyography (train-of-four [TOF] stimulation). A statistically significant fade (reduction of the second maneuver from the first maneuver) of FVC, FEV(1), FIV(1), PEF, and PIF was observed during neuromuscular blockade. With peak relaxation (TOF ratio, 0.5) fade amounted to medians of 10% (interquartile range [IQR], 9 to 23%), 7% (IQR, 2 to 16%), 31 (IQR, 19 to 47%), 9% (IQR, 3 to 24%), and 30% (IQR, 5 to 43%), respectively. A fade of >or= 10% was always associated with a clinically relevant (>or= 10%) FVC reduction from baseline (ie, FVC before rocuronium administration). However, FVC reduction from baseline was still present in 23% of measurements without a relevant FVC fade. CONCLUSIONS: A clinically relevant fall (fade) in FVC from the first to the second value during or after neuromuscular blockade suggests impaired pulmonary function and may be due to muscle paralysis. For this reason, the first (best) FVC value may overestimate pulmonary function and expose the patient to an unidentified risk.     

Genomewide production of multipurpose alleles for the functional analysis of the mouse genome

A type of retroviral gene trap vectors has been developed that can induce conditional mutations in most genes expressed in mouse embryonic stem (ES) cells. The vectors rely on directional site-specific recombination systems that can repair and re-induce gene trap mutations when activated in succession. After the gene traps are inserted into the mouse genome, genetic mutations can be produced at a particular time and place in somatic cells. In addition to their conditional features, the vectors create multipurpose alleles amenable to a wide range of post-insertional modifications. Here we have used these directional recombination vectors to assemble the largest library of ES cell lines with conditional mutations in single genes yet assembled, presently totaling 1,000 unique genes. The trapped ES cell lines, which can be ordered from the German Gene Trap Consortium, are freely available to the scientific community.     

The crystal structure of avian CD1 reveals a smaller,more primordial antigen-binding pocket compared to mammalian CD1

The molecular details of glycolipid presentation by CD1 antigen-presenting molecules are well studied in mammalian systems. However, little is known about how these non-classical MHC class I (MHCI) molecules diverged from the MHC locus to create a more complex, hydrophobic binding groove that binds lipids rather than peptides. To address this fundamental question, we have determined the crystal structure of an avian CD1 (chCD1–2) that shares common ancestry with mammalian CD1 from ≈310 million years ago. The chCD1–2 antigen-binding site consists of a compact, narrow, central hydrophobic groove or pore rather than the more open, 2-pocket architecture observed in mammalian CD1s. Potential antigens then would be restricted in size to single-chain lipids or glycolipids. An endogenous ligand, possibly palmitic acid, serves to illuminate the mode and mechanism of ligand interaction with chCD1–2. The palmitate alkyl chain is inserted into the relatively shallow hydrophobic pore; its carboxyl group emerges at the receptor surface and is stabilized by electrostatic and hydrogen bond interactions with an arginine residue that is conserved in all known CD1 proteins. In addition, other novel features, such as an A′ loop that interrupts and segments the normally long, continuous α1 helix, are unique to chCD1–2 and contribute to the unusually narrow binding groove, thereby limiting its size. Because birds and mammals share a common ancestor, but the rate of evolution is slower in birds than in mammals, the chCD1–2-binding groove probably represents a more primordial CD1-binding groove.     

Binding of the partially purified glucocorticoid receptor of rat liver to chromatin and DNA

The binding of the glucocorticoid receptor of rat liver to chromatin and DNA has been studied with crude and partially purified preparations of cytosol receptor labelled with [³H]-triamcinolone acetonide in vitro. The use of crude preparations of receptor and increasing protein concentrations leads to an apparent saturation of chromatin and DNA, suggesting a limited number of high affinity nuclear acceptor sites for the receptor. Appropriate controls indicate that the observed saturability of chromatin acceptor sites is due to the presence in crude receptor preparations of heat-stable protein factors which interfere with the binding of the receptor to the genome; whereas the apparent saturation of DNA is due to contamination with deoxyribonucleases.If the activated complex of receptor and triamcinolone acetonide (R-TA) is partially purified to a step where it is free from nucleases and inhibitors, its binding to both chromatin and DNA is linearly dependent on the concentration of free (R-TA) in the incubation medium. There is no absolute specificity with respect to the source of DNA or chromatin, although liver chromatin has considerably higher receptor binding capacity than chromatin from avian erythrocytes.The rate kinetics of association and dissociation for the binding of (R-TA) to DNA and chromatin are very similar, but DNA exhibits a 10-fold higher receptor binding capacity than chromatin. These data, in conjunction with the effect of poly-(D)-lysine and NaCl on the binding of (R-TA) to chromatin and DNA, suggest that most of the receptor molecules bound to chromatin in vitro interact with the ‘accessible’ DNA stretches. Although a small population of receptor molecules may bind specifically to target tissue genome, the detection of these specific sites against the background of unspecific binding is not possible with unfractionated chromatin or DNA preparations.