Restenosis after coronary angioplasty: An overview Califf, Robert M.; Fortin, Donald F.; Frid, David J. ...
Journal of the American College of Cardiology,
05/1991, Volume:
17, Issue:
6
Journal Article, Conference Proceeding
Peer reviewed
Open access
Despite substantial basic and clinical efforts to address the problem of restenosis after percutaneous coronary intervention, effective preventive therapies have not yet been developed. Nevertheless, ...the accumulated information has provided much insight into the process of restenosis in addition to allowing standards to be developed for adequate clinical trials.
The pathophysiology of restenosis increasingly appears to be distinct from that of primary atherosclerosis. Restenosis involves elastic recoil, incorporation of thrombus into the lesion and fibrocellular proliferation in varying degrees in different patients. Lack of an animal model that satisfactorily mimics restenosis is a major impediment to further understanding of the process. Clinical studies are hampered by difficulties in finding a single unifying definition of restenosis and by variable methods of reporting follow-up. Reporting of clinical outcomes of all patients in angiographic substudies would allow a more satisfactory interpretation of the results of clinical trials. Current noninvasive test results are not accurate enough to substitute for angiographic and clinical outcome data in intervention trials.
In the majority of observational studies, only diabetes and unstable angina have emerged as consistently associated with restenosis; whereas most of the standard risk factors for atherosclerosis have a less consistent relation. Disappointingly, the new atherectomy and laser technologies have not affected restenosis rates. The one possible exception is coronary stenting, as a result of the larger luminal diameter achieved by the placement of the stent.
In conclusion, although substantial continued effort is necessary to explore the basic aspects of cellular proliferation and mechanical alteration of atherosclerotic vessels, attention to the principles of clinical trials and observation are required to detect the impact of risk factors and interventions on the multifactorial problem of restenosis. Adequate sample sizes, collection of clinical and angiographic outcomes and factorial study designs hold promise for unraveling this important limitation of percutaneous intervention.
74 piston, gravity and jumbo Kasten cores were collected from channel and canyon systems draining the northern California continental margin to investigate the record of periodic Holocene turbidites ...for possible connection to large magnitude earthquakes on the adjacent Northern San Andreas Fault. Poorly known channel systems were mapped with multibeam sonar to define pathways and channel confluences. Cores sampled all major and many minor channel systems extending from Cape Mendocino to just north of Monterey Bay. Sampling both along and across channels was done and particular attention was paid to channel confluences, as these areas afford opportunities to test for synchronous triggering of turbidity currents. While at sea, all cores were scanned using a GEOTEK multisensor core logger (MSCL), which collects high-resolution photography, P-wave velocity, gamma-ray density, and magnetic susceptibility data from the unsplit cores. Lithology was logged visually, and cores were later imaged with X-radiography.
We use 14C ages, relative dating tests at channel confluences, and stratigraphic correlation using physical properties to determine whether turbidites deposited in separate channel systems are correlative, implying they were triggered by a common event. These tests can, in most cases, separate earthquake-triggered turbidity currents from other possible sources. The late Holocene turbidite record off northern California passes these tests for synchronous triggering, and can be correlated with multiple proxies from site to site between Noyo Channel and the latitude of San Francisco. Preliminary comparisons of our event ages with existing and in progress work at onshore coastal sites show good correlation, further circumstantial evidence that the offshore record is primarily earthquake generated. During the last ∼2800 yr, 15 turbidites are recognized, including the great 1906 earthquake. Their chronology establishes an average repeat time of ∼200 yr, similar to the onshore value of ∼230 yr. Along-strike correlation suggests that at least 8 of the youngest 10 of these events ruptured the 320 km distance from the Mendocino Triple Junction to near San Francisco.
Patients with cholestasis-lymphedema syndrome (CLS) suffer severe neonatal cholestasis that usually lessens during early childhood and becomes episodic; they also develop chronic severe lymphedema. ...The genetic cause of CLS is unknown. We performed a genome screen, using DNA from eight Norwegian patients with CLS and from seven unaffected relatives, all from an extended pedigree. Regions potentially shared identical by descent in patients were further characterized in a larger set of Norwegian patients. The patients manifest extensive allele and haplotype sharing over the 6.6-cM
D15S979–D15S652 region: 30 (83.3%) of 36 chromosomes of affected individuals carry a six-marker haplotype not found on any of the 32 nontransmitted parental chromosomes. All Norwegian patients with CLS are likely homozygous for the same disease mutation, inherited from a shared ancestor.
Acetaminophen (APAP) is known to cause centrilobular hepatic necrosis under overdose conditions. This is thought to be mediated via the P450-generated reactive intermediate N-acetyl-p-benzoquinone ...imine (NAPQI). Initially, NAPQI is detoxified by conjugation with glutathione (GSH), but once GSH is depleted, NAPQI reacts more extensively with hepatic proteins leading to hepatocellular damage. The P450 isoforms thought to be responsible for APAP hepatotoxicity in humans are CYP2E1, CYP1A2, and CYP3A4, and thus, we have investigated the effect of murine Cyp1a2 on APAP hepatotoxicity using Cyp1a2 knockout mice (Liang et al., Proc. Natl. Acad. Sci. USA 93, 1671-1676, 1996). Doses of 250 mg/kg were markedly hepatotoxic in these mice, and surprisingly, deaths only occurred in the knock-out and heterozygote mice over a 24-h period after dosing. Furthermore, there were no significant differences among survivors of any genotype in serum ALT concentrations, a well correlated indicator of APAP hepatotoxicity in mice. Finally, no differences were observed in the urinary metabolites excreted ove the 24-h period, including those derived from GSH conjugation of the major reactive metabolite NAPQI. Consistent with the effects on hepatotoxicity and metabolism, 2 h after hepatotoxic doses (500 mg/kg, i.p.) of APAP no significant differences were observed in total whole liver homogenate nonprotein thiol concentrations among the three genotypes even though hepatic thiols were decreased compared to control animals (> 90%). In addition, when the liver cytosol and microsome samples were examined by immunoblotting for the presence of APAP-protein adducts using a specific antiserum, there were no observable differences in either the intensity of staining or in the spectrum of adducts formed between APAP-dosed mice of any genotype. The cumulative data suggest that Cyp1a2 doses not play a significant role in APAP hepatotoxicity in these mice.
Host defenses against infection are profoundly compromised in HIV-infected hosts due to progressive depletion of CD4+ T lymphocytes and defective cell-mediated immunity. Although recent advances in ...antiretroviral therapy can dramatically lower HIV viral load, blood CD4+ T lymphocytes are not restored to normal levels. Therefore, we investigated mechanisms of host defense other than those involving CD4+ T lymphocytes against a common HIV-related opportunistic infection, Pneumocystis carinii (PC) pneumonia. Using CD4-depleted mice, which are permissive for chronic PC infection, we show that up-regulation of murine IFN-gamma by gene transfer into the lung tissue results in clearance of PC from the lungs in the absence of CD4+ lymphocytes. This resolution of infection was associated with a >4-fold increase in recruited CD8+ T lymphocytes and NK cells into the lungs. The role of CD8+ T cells as effector cells in this model was further confirmed by a lack of an effect of IFN-gamma gene transfer in scid mice or mice depleted of both CD4+ and CD8+ T cells. Cytokine mRNA analysis revealed that recruited, lung-derived CD8+ T cells had greater expression of IFN-gamma message in animals treated with the IFN-gamma gene. These results indicate that CD8+ T cells are capable of clearing PC pneumonia in the absence of CD4+ T cells and that this host defense function of CD8+ T cells, as well as their cytokine repertoire, can be up-regulated through cytokine gene transfer.
Dead Run is a 14.3 km2 urban drainage basin, which is a tributary to the Gwynns Falls, the principal study watershed of the Baltimore Ecosystem Study. Hydrologic response in urban watersheds is ...examined through analyses of rainfall and discharge observations from the Dead Run watershed during a 6 month period beginning in June of 2003. Rainfall variability for flash flood-producing storms in Dead Run can be quite large when viewed from a Euclidean perspective. When viewed from the perspective of a distance metric imposed by the drainage network of Dead Run, however, the spatial variability of rainfall is small. The drainage network structure diminishes the effects of spatial rainfall variability for storm event hydrologic response, resulting in Dead Run exhibiting striking uniformity of response to storms with contrasting spatial distribution of rainfall. There is large storm-to-storm variation in the event water balance of Dead Run. Variation is linked to antecedent soil moisture (from the pervious portion of the watershed underlain by urban soils), rainfall variability, and spatial heterogeneity of runoff production.
In many diseases, tissue hypoxia occurs in conjunction with other inflammatory processes. Since previous studies have demonstrated a role for leukocytes in ischemia/reperfusion injury, we ...hypothesized that endothelial hypoxia may ``superinduce'' expression of an important leukocyte adhesion molecule, E-selectin (ELAM-1, CD62E). Bovine aortic endothelial monolayers were exposed to hypoxia in the presence or absence of tumor-necrosis factor α (TNF-α ) or lipopolysaccharide (LPS). Cell surface E-selectin was quantitated by whole cell ELISA or by immunoprecipitation using polyclonal anti-E-selectin sera. Endothelial mRNA levels were assessed using ribonuclease protection assays. Hypoxia alone did not induce endothelial E-selectin expression. However, enhanced induction of E-selectin was observed with the combination of hypoxia and TNF-α (270% increase over normoxia and TNF-α ) or hypoxia and LPS (190% increase over normoxia and LPS). These studies revealed that a mechanism for such enhancement may be hypoxia-elicited decrements in endothelial intracellular levels of cAMP (<50% compared with normoxia). Addition of forskolin and isobutyl-methyl-xanthine during hypoxia resulted in reversal of cAMP decreases and a loss of enhanced E-selectin surface expression with the combination of TNF-α and hypoxia. We conclude that endothelial hypoxia may provide a novel signal for superinduction of E-selectin during states of inflammation.
The speciation of chromium in overlayers on atomically clean surfaces of single crystal magnetite (Fe
3O
4) and hematite (α-Fe
2O
3) were studied using Cr L-edge, Fe L-edge, and O K-edge X-ray ...absorption spectra collected with synchrotron radiation. The overlayers were produced by reaction of the surfaces with 5
mM or 50
μM Na
2CrO
4 aqueous solutions in a N
2-filled glove bag in opaque containers at exposure times ranging from 1
min to over 60
min. X-ray absorption data were acquired using total electron yield and more surface-sensitive Auger yield detection. O 1s, Cr 2p, and Fe 2p photoemission spectra taken on the same samples corroborate findings from the Cr and Fe L-edge and O K-edge spectroscopy, and show that the outermost portion of the overlayers contains mostly Cr with little if any Fe, and are ∼15
Å thick for the high concentration exposures. The thickness of the overlayer increases with Cr(VI) solution concentration and exposure time up to this maximum thickness. The presence of chemically shifted components in the O 1s photoemission spectra indicates OH
− ligands around Cr and Fe. Comparison of the Cr L-edge X-ray absorption spectra of crystalline PbCrO
4, which contains tetrahedrally coordinated Cr(VI), and crystalline FeCr
2O
4, which contains octahedrally coordinated Cr(III), with Cr L-edge spectra of the aqueous Cr(VI)-exposed iron oxide surfaces shows that Cr(VI) is reduced to Cr(III) on magnetite (111). For magnetite (111) surfaces reacted with 5
mM solutions for 10
min or longer, a significant amount of Cr(VI) is present in the outermost portion of the overlayer, indicating that Cr(VI) reduction is incomplete. Complete reduction of Cr(VI) was found on magnetite (111) exposed to the 50
μM Na
2CrO
4 solution for 1
min or longer, indicating rapid reaction kinetics. We find that while Cr adsorbed on the (11̄02) surface of hematite (Fe
2O
3) remains in the original Cr(VI) form, small amounts are reduced to Cr(III) on (0001) hematite surfaces. This difference is due to the presence of Fe(II) on the (0001) hematite surfaces produced during annealing in a vacuum environment. These results corroborate earlier studies which have demonstrated that oxides containing Fe(II) in the near-surface region can reduce Cr(VI) to Cr(III), and they show that the overlayer consists of a mixture of FeOOH- and CrOOH-like phases, with the latter concentrated in the outermost 7–15
Å and the former concentrated in the innermost portion of the passivating overlayer. At a thickness of >15
Å, the passivating overlayer causes a reduction in the kinetics of the Cr(VI)+3Fe(II)=Cr(III)+3Fe(III) redox reaction.
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