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Biomedical subjects

J Moses

Publications and source records attributed to J Moses.

At least 37 records · Page 2Linked to original sources

Biosynthesis of decorin and glypican.

Decorin and glypican are two examples of exclusively chondroitin/dermatan sulfate and heparan sulfate-substituted proteoglycans, respectively. Decorin is a secretory product, whereas glypican is linked to membrane lipids via a glycosyl-phosphatidyl-inositol (GPI) anchor. The nascent decorin protein enters the lumen of the ER, whereas that of glypican is transferred to the preformed GPI-anchors. Both types of glycosaminoglycuronans are initiated on Ser residues located in special consensus sequences, and the first glycosylation steps constitute a common pathway: the generation of the linkage region GlcA-Gal-Gal-Xyl-Ser<. The nature of the enzymes involved will be reviewed with special emphasis on the recently discovered transient 2-phosphorylation of xylose. The initiation enzymes (betaGalNAc-T1 and alphaGlcNAc-T1) then use these tetrasaccharide primers for either chondroitin or heparan sulfate assembly. The selection mechanism is not yet fully understood. The transferases that form the linkage-region and add the first hexosamine, as well as the uronosyl C-5 epimerases, appear to be products of single genes, but many isoforms of the copolymerases and sulfotransferases forming the repetitive part of the glycan chains are currently being discovered. When these enzymes work together, the fine structure of the glycosaminoglycuronans appears to be generated through the selective expression of isoforms that only operate in certain structural contexts. During heparan sulfate assembly, generation of GlcNH(2) as a permanent feature is now well recognised. Studies on glypican-1 glycoforms that recycle suggest that heparan sulfate chains are degraded by endoheparanase at or near GlcNH(2) residues, followed by deaminative cleavage catalysed by NO-derived nitrite. Chain-truncated glypican-1 can serve as a precursor for the reformation of a proteoglycan with full-size chains. Regulation of biosynthesis can be exercised at several levels, such as expression of the core protein, selection for chondroitin or heparan sulfate assembly, expression of modifying enzymes, and degradation and remodelling. Cytokines, growth factors, NO and polyamines may have regulatory roles.

Animals↗

Atherectomy plus stenting: what do we gain?

Coronary stents have improved the short and long-term outcomes of selected patients undergoing catheter-based coronary interventions. However, the use of these devices in complex coronary lesions has also created an incessant form of in-stent restenosis that still defies treatment. Plaque burden has been recognized as an important factor that may incite neo-intimal proliferation after stent implantation. Prospective non-randomized experience has shown that plaque removal prior to stent implantation using directional atherectomy is a promising approach to reduce restenosis in selected patients. However, the proof of concept awaits the results of the randomized trials. Ultimately, the clinical utility of this approach will depend upon: (1) further improvements on the current directional atherectomy device; (2) minimizing the incidence of non-Q-wave myocardial infarction with selective use of IIb-IIIa platelet receptor antagonists or distal protection devices; (3) targeting patients at high risk for restenosis in whom efficient debulking is feasible such as non-calcified lesions in vessels >2.75 mm and <3.5 mm in diameter that require long stents, aorto-ostial lesions, bifurcational lesions, and chronic total occlusions.

Atherectomy, Coronary↗

Heparin infusion prior to stenting (HIPS) trial: final results of a prospective, randomized, controlled trial evaluating the effects of local vascular delivery on intimal hyperplasia.

BACKGROUND: Local delivery of pharmacologic agents or genes at the site of angioplasty is a promising approach to reduce restenosis. However, there are unresolved questions concerning the safety and feasibility of local vascular delivery in clinical practice as well as the efficacy of delivered drug. To this end, the safety, feasibility, and efficacy of local delivery of heparin were evaluated in the Heparin Infusion Prior to Stenting (HIPS) trial. METHODS AND RESULTS: A total of 179 patients were enrolled in this multicenter, randomized, prospective, core laboratory-evaluated trial. Patients were randomly assigned to 5000 U heparin either administered to the coronary artery lumen or infused into the arterial wall immediately after angioplasty and before stent placement. End points included procedural events and clinical, angiographic, and intravascular ultrasound events at 6 months. Patient groups were evenly matched. There was no difference in the incidence of arterial injury, defined as an increase in arterial dissection, acute closure, or decrease in Thrombolysis In Myocardial Infarction grade blood flow in the group receiving local delivery. At follow-up there was no difference in the major adverse event rate between intraluminal (22.7%) and local groups (24.7%). There was no difference between intraluminal and local therapy in the angiographic in-stent restenosis rate (12.5%, 12.7%) or the in-stent volumetric analysis by intravascular ultrasound (IVUS) (37.19 +/- 20. 86 mm(3) vs 43.79 +/- 25.52 mm(3)). CONCLUSIONS: Local delivery of 5000 U heparin into the arterial wall before stent implantation is safe and feasible. There was not a favorable effect of locally delivered heparin on clinical, angiographic, or IVUS end points of restenosis. The use of IVUS to measure volume of intimal hyperplasia in a multicenter, core laboratory-controlled trial is feasible.

Blood Flow Velocity↗

Personnel exposure during gamma endovascular brachytherapy.

PURPOSE: The use of 192Ir brachytherapy for the treatment of in-stent restenosis of the coronary arteries has shown promising clinical results. This paper investigates the radiation exposure of catheterization laboratory staff associated with the performance of this procedure. METHODS AND MATERIALS: Cath lab staff were monitored using personal monitors (shielded against fluoroscopic x-rays) during the performance of eleven cases using nominal 10 GBq 192Ir sources. Staff positions in the lab were simultaneously tracked by video cameras. Direct measurements were also made using a survey meter. Treatments were administered in a conventional cardiac-catheterization-laboratory. RESULTS: The dosimeter readings were analyzed in combination with the radiation survey and time motion survey. Brachytherapy procedural times for the cardiologist, oncologist, physicist, and angiographic assistants were, respectively, 26 +/- 24, 401 +/- 132, 486 +/- 148, and 7 +/- 13 s per case (mean +/- standard deviation). Readings of the personnel monitors were low. Credible upper limits of the respective doses are estimated to be less than 10, 10, 7, and 5 microSv per procedure. Auxiliary shields reduced the dose to individuals located outside of the catheterization laboratory to less than 0.5 microSv per procedure. CONCLUSIONS: The average radiation dose received by laboratory personnel during a representative 192Ir endocoronary brachytherapy procedure is estimated to be less than 0.1% of the NCRP recommended annual radiation worker's Maximum Permissible Dose (1% of the general public's MPD). This level is justifiable as long as the use of 192Ir benefits patients by producing an improved clinical outcome relative to the use of a less penetrating radionuclide or the application of alternative therapies. Further optimization of the delivery procedure is expected to reduce staff dose.

Brachytherapy↗

Multivessel coronary stenting: predictors of early and late outcome.

BACKGROUND: At present, only few data are available on the early and late outcome following multivessel coronary stenting. Of note, in these studies, the left anterior descending (LAD) artery was treated in less than 40% of cases. These patients may not fully represent the population commonly referred for surgical revascularization. METHODS: In-hospital and long-term (18 +/- 4 months) events were evaluated in 272 consecutive patients who had multivessel stent implantation including the LAD artery in each case. All clinical, angiographic, and procedural variables were analyzed to identify the predictors of acute and long-term major adverse coronary events. RESULTS: Eighteen patients (6.6%) had in-hospital major adverse coronary events (death 0.7%, coronary artery bypass grafting 0.4%, and myocardial infarction 6.3%). Acute and subacute stent thrombosis rates were 1.5 and 1.1%, respectively. At 18 +/- 4 months, event-free survival was 71%. Target lesion revascularization was performed in 54 (20%) patients (42 coronary angioplasty and 12 coronary artery bypass grafting). The jeopardy score was the predictor of in-hospital major adverse coronary events (p = 0.016, odds ratio 1.34, 95% confidence interval 1.05-1.69), and diabetes mellitus was the predictor of long-term major adverse coronary events (p = 0.027, odds ratio 2.80, 95 % confidence interval 1.12-6.96). CONCLUSIONS: Multivessel coronary stent implantation with treatment of the LAD artery in all instances is a safe procedure with low acute and long-term major adverse coronary events. The risk-benefit ratio must be assessed carefully for each patient, particularly taking into account the jeopardy score and the presence of diabetes mellitus.

Aged↗

The Efficacy of Directional Atherectomy Prior to Stent Implantation.

Coronary stents have improved the short- and long-term outcomes of patients undergoing catheter-based coronary interventions. However, the use of these devices in complex coronary lesions has also created an incessant form of in-stent restenosis that still defies treatment. Plaque burden has been consistently and reproducibly recognized as an important factor that may incite neointimal proliferation after stent implantation. Prospective nonrandomized experience has shown that plaque removal prior to stent implantation using directional atherectomy is a promising approach to reduce restenosis in selected patients. However, the proof of concept awaits the results of the randomized trials. Ultimately, the clinical use (safety and efficacy) of this approach will depend on 1) further improvements on the current directional atherectomy device to make it user friendly; 2) minimizing the incidence of non-Q-wave myocardial infarction with selective use of IIb-IIIa platelet receptor antagonists or distal protection devices; and 3) targeting patients at high risk for restenosis in whom efficient debulking is feasible. This would include patients who have noncalcified lesions in vessels greater than 2.75 mm but less than 3.5 mm in diameter that require a long stent or multiple stents, aorto-ostial lesions, bifurcational lesions, and chronic total occlusions.

Journal Article↗

Procedural and late outcomes following MULTI-LINK DUET coronary stent deployment.

The MULTI-LINK DUET is the next generation MULTI-LINK stent with modified strut geometry. Safety and efficacy of the MULTI-LINK DUET were evaluated in a prospective multicenter registry and were compared with prior MULTI-LINK stent experience from the ASCENT randomized trial. A total of 270 patients received 302 MULTI-LINK DUET stents and were evaluated using a composite primary end point of major cardiac events (death, Q-wave and non-Q-wave myocardial infarction, and requirement for coronary revascularization) attributable to the target stenosis cumulative to 30 days following enrollment. Quantitative coronary angiography was performed at a mean follow-up of 6 +/- 2 (+/-SD) months. No difference in primary end point or in angiographic restenosis to 6 months was observed between MULTI-LINK DUET and MULTI-LINK experiences. The MULTI-LINK DUET demonstrated improved device and procedural success, less postprocedural in-stent stenosis, larger postprocedural minimal lumen diameter, and fewer postprocedural marginal dissections compared with the MULTI-LINK stent. Multivariate regression modeling identified stent length, diabetes mellitus, poststent minimal lumen diameter, lesion eccentricity, and current smoking as independent predictors of in-stent restenosis. Thus, the MULTI-LINK DUET Registry demonstrates enhanced procedural performance with clinical and angiographic outcomes similar to those previously observed for the MULTI-LINK stent in the ASCENT randomized trial.

Aged↗

Hormone-neurotransmitter interactions in the control of sexual behavior.

The stimuli from a receptive female and/or copulation itself leads to the release of dopamine (DA) in at least three integrative hubs. The nigrostriatal system promotes somatomotor activity; the mesolimbic system subserves numerous types of motivation; and the medial preoptic area (MPOA) focuses the motivation onto specifically sexual targets, increases copulatory rate and efficiency, and coordinates genital reflexes. The previous (but not necessarily concurrent) presence of testosterone is permissive for DA release in the MPOA, both during basal conditions and in response to a female. One means by which testosterone may increase DA release is by upregulating nitric oxide synthase, which produces nitric oxide, which in turn increases DA release. Hormonal priming in females may also increase DA release in the MPOA, and copulatory activity may further increase DA levels in females. One of the intracellular effects of stimulation of DA D1 receptors in the MPOA of male rats may be increased expression of the immediate-early gene c-fos, which may mediate longer term responses to copulation. Furthermore, increased sexual experience led to increased immunoreactivity to Fos, the protein product of c-fos, following copulation to one ejaculation. Another intracellular mediator of DA's effects, particularly in castrates, may be the phosphorylation of steroid receptors. Finally, while DA is facilitative to copulation, 5-HT is generally inhibitory. 5-HT is released in the LHA, but not in the MPOA, at the time of ejaculation. Increasing 5-HT in the LHA by microinjection of a selective serotonin reuptake inhibitor (SSRI) increased the latency to begin copulating and also the latency to the first ejaculation, measured from the time the male first intromitted. These data may at least partially explain the decrease in libido and the anorgasmia of people taking SSRI antidepressants. One means by which LHA 5-HT decreases sexual motivation (i.e. increases the latency to begin copulating) may be by decreasing DA release in the NAcc, a major terminal of the mesolimbic system. Thus, reciprocal changes in DA and 5-HT release in different areas of the brain may promote copulation and sexual satiety, respectively.

Animals↗

Catheter-based reperfusion of unprotected left main stenosis during an acute myocardial infarction (the ULTIMA experience). Unprotected Left Main Trunk Intervention Multi-center Assessment.

The ULTIMA registry was a prospective, multicenter, international registry of 277 patients who underwent percutaneous coronary interventions of unprotected left main trunk stenosis. The 40 patients who underwent an emergency percutaneous left main intervention for acute myocardial infarction are the focus of this study. We compared the results of primary angioplasty with primary stenting, characterizing both the short-term (in-hospital) and long-term (12-month) outcomes. Of the 40 patients, 23 underwent primary angioplasty, whereas 17 underwent primary stenting. The angiographic success rate was an 88% for the cohort. The in-hospital death or coronary artery bypass grafting rate was 65% for the entire group, 74% for the percutaneous transluminal coronary angioplasty group (PTCA), and 53% for the stent group (p = 0.2). The in-hospital death rate was 55% for the entire cohort, 70% for the PTCA group, and 35% for the stent group (p = 0.1). The 12-month rate of death or bypass surgery was 83% and 58% for the PTCA and stent groups, respectively (p = 0.047). The 12-month survival rate was 35% and 53% for the PTCA and stent groups, respectively (p = 0.18). Bypass surgery was required in 6 patients in the PTCA group and 2 patients in the stent group (p = 0.07). Patients undergoing percutaneous interventions for unprotected left main myocardial stenosis during an acute myocardial infarction are critically ill; an initial percutaneous revascularization approach appears feasible and may be the preferred revascularization strategy. Primary stenting was associated with improved clinical outcomes.

Aged↗

Does the specific intravascular ultrasound criterion used to optimize stent expansion have an impact on the probability of stent restenosis?

Intravascular ultrasound (IVUS) imaging has been used to optimize stent implantation in coronary arteries, but the criteria used were chosen on an empiric basis. The aim of this study was to determine whether any of these criteria have an independent role in predicting the probability of freedom from restenosis. The study population consisted of 425 patients (496 lesions) who underwent angiographically successful IVUS-guided stenting. Five IVUS criteria were studied: (1) intrastent minimal lumen cross-sectional area (ISMLCSA) > or =9 mm2; (2) ISMLCSA (> or =9 mm2 and > or =80% of average reference lumen cross-sectional area [CSA]); (3) ISMLCSA > or =90% of average reference lumen CSA; (4) ISMLCSA > or =90% of distal reference lumen CSA; and (5) ISMLCSA > or =55% of average reference vessel CSA. These criteria were met in 33%, 29%, 68%, 82%, and 69% of lesions, respectively. Angiographic follow-up was performed in 335 of 421 eligible patients (80%) at 5.3 +/- 2.7 months. An absolute ISMLCSA > or =9 mm2 was associated with the lowest restenosis, but this criterion was primarily achieved in large vessels. The only criterion that was associated with higher probability of freedom from restenosis independently from vessel size was an ISMLCSA > or =55% of average reference vessel CSA. Therefore, when IVUS is used to guide stent implantation an effort should be made to achieve the largest lumen safely possible. An ISMLCSA > or =55% of the average reference vessel CSA seems to be the most appropriate criterion in terms of frequency of achievement and in terms of increasing the probability of freedom from restenosis.

Coronary Angiography↗

Do new devices add to the results of PTCA in acute myocardial infarction?

Several randomized trials have established that timely mechanical reperfusion with the use of balloon angioplasty is superior to thrombolytic therapy in patients with acute myocardial infarction. Furthermore, recent data from prospective randomized trials suggest that primary stent implantation may further improve the results of balloon angioplasty by reducing the need for repeat interventions at follow-up. The role of IIb-IIIa platelet receptor antagonists as adjunctive therapy to catheter-based coronary interventions in acute myocardial infarction is promising, but the incremental benefit that these agents add to stent implantation awaits the results of dedicated randomized trials. Mechanical thrombolysis or thrombectomy devices may have a role in a minority of patients with large thrombus burden.

Angioplasty, Balloon, Coronary↗

A nitric oxide synthesis inhibitor administered into the medial preoptic area increases seminal emissions in an ex copula reflex test.

Nitric oxide synthesis inhibitors, when administered systemically or into the ventricles of the brain, affect several indices of male sexual behavior. Some of the systemic effects are assumed to be due to local vasoconstriction at the penis. Others are suggested to be mediated within the brain. In these experiments, the nitric oxide synthesis inhibitor L-NMMA, and its less active enantiomer, D-NMMA, were microinjected into the medial preoptic area of male rats. In an ex copula test of genital reflexes, L-NMMA increased the number of seminal emissions, while D-NMMA had no effect. These results are consistent with the hypothesis that nitric oxide is a tonic inhibitor of sympathetic nervous system tone, possibly in part through an influence on dopamine synthesis or release.

Animals↗

Structural aspects of human IgM antibodies expressed in chronic B lymphocytic leukemia.

BACKGROUND: Malignant B cells from patients with chronic B lymphocytic leukemia (B CLL) generally express both surface IgM and the pan T cell antigen CD5, a characteristic of the B1 population of B lymphocytes. The IgM on the surface of these B CLL cells is frequently polyreactive with respect to its capacity to recognize multiple structurally dissimilar antigens (Ag). OBJECTIVES: To understand the structural characteristics of the polyreactive binding sites of human IgM molecules expressed on B CLL cells by: (1) analyzing the nucleotide and protein sequences of the variable (V) domains of five IgM molecules expressed in cases of B CLL and; (2) utilizing these sequences to generate three-dimensional (3D) models of Fv (VL - VH) molecules. STUDY DESIGN: Peripheral blood leukocytes obtained from five cases of B CLL were tested for polyreactive binding properties by assessing their capacity to bind mouse IgG by indirect immunofluorescence. The V region genes of light and heavy chains were amplified using the polymerase chain reaction, subsequently cloned and their nucleotide sequences obtained. Translated amino acid sequences of the V domains were used to generate homology models of the Fv molecules. RESULTS: Low affinity binding of mouse IgG was demonstrated for all B CLL samples examined, confirming the polyreactive nature of the IgM expressed on these cells. There was an absence or minimal mutation within V region genes when compared to germline Ig genes. Junctional diversity was not observed for VL regions, although truncations and insertions were frequent in D minigenes of VH regions. The binding sites were predicted to form either relatively flat surfaces with occasional protrusions or cavities at the VL - VH domain interface. Aromatic side chains covered a large proportion of the potential binding surfaces in the models of B CLL Fv components. DISCUSSION: Primary DNA sequences can be categorized as germline, suggesting that the B cells involved in B CLL are germline or naive in origin. The medium to large HCDR3s provide the majority of probable contact residues for antigens. While prominent aromatic residues are likely to engage in binding patterns which are conserved (e.g. mouse Ig reactivity), the diverse binding sites predicted for B CLL-derived IgMs also have properties which are conducive to polyreactive antigen binding.

Amino Acid Sequence↗

Initiation of galactosaminoglycan biosynthesis. Separate galactosylation and dephosphorylation pathways for phosphoxylosylated decorin protein and exogenous xyloside.

By using various radiolabelled precursors, glycosylation and phosphorylation of decorin in a rat fibroblast cell line was investigated in the presence of increasing concentrations of p-nitrophenyl-O-beta-d-xylopyranoside. Decorin core protein glycanation was suppressed to approximately 25% of the normal level in the presence of 2 mm and 3 mm xyloside. Glycans/saccharides were released from the core protein and size-separated by gel chromatography. The intracellular decorin obtained from cells treated with 2 mm xyloside was substituted with Xyl and also with Gal-Xyl and Gal-Gal-Xyl, but not with longer saccharides. Only the trisaccharide contained an almost fully phosphorylated Xyl. We conclude that galactosylation of endogenous, xylosylated decorin and exogenous xyloside probably follow separate pathways or that xylosides and early decorin glycoforms are kept separated. At the addition of the first glucuronic acid the two pathways seem to merge and dephosphorylation of decorin takes place. Xyloside-primed and secreted galactosaminoglycan chains produced simultanously retained phosphorylated Xyl. Inadequate dephosphorylation could be due to excess substrate or to a short transit.time. As shown previously [Moses, J., Oldberg, A., Eklund, E. & Fransson, L.-A. (1997) Eur. J. Biochem. 248, 767-774], brefeldin A-arrested decorin is substituted with the linkage-region extended with an undersulphated and incomplete galactosaminoglycan chain. In cells treated with this drug, xylosides were unable to prime galactosaminoglycan synthesis and unable to inhibit glycosylation and phosporylation of decorin.

Animals↗

Birth weight of women with gestational diabetes.

OBJECTIVE: Epidemiological observations have suggested a relationship between type 2 diabetes and a low birth weight. However, there are many confounding variables and problems with retrospective data collection. Women with gestational diabetes mellitus (GDM), who are likely to develop type 2 diabetes in the future, may help clarify these observations. RESEARCH DESIGN AND METHODS: Consecutive women with GDM (n = 138) were included in the study if they had a singleton pregnancy delivered between 37 and 41 weeks of gestation, if they had themselves been born in the local hospital, and if their own delivery data were available. With respect to their own births, a matched group was obtained by considering the next female delivery of the same gestational age. RESULTS: For women with GDM, the mean (+/- 1 SD) birth weight was 3,293 +/- 493 g and the ponderal index was 27.0 +/- 2.4. Their values were not significantly different from the matched group, which had a birth weight of 3,315 +/- 460 g and a ponderal index of 27.0 +/- 2.5. After adjusting for the gestational age of delivery, the birth weight of women with GDM did not show a U-shaped distribution. CONCLUSIONS: After adjustment for the gestational age of delivery, women with GDM do not themselves have either a lower or higher birth weight than a matched group. These data suggest that women with GDM are either not a good surrogate for investigating the relationship between birth weight and type 2 diabetes or that correction for the gestational age of delivery removes the most important confounding variable. It is also possible that modern dietary changes may have altered the relationship.

Adult↗

Stenting after optimal lesion debulking (sold) registry. Angiographic and clinical outcome.

BACKGROUND: Coronary stenting has reduced restenosis in focal de novo lesions, but its impact has been less pronounced in complex lesion subsets. Preliminary data suggest a role for plaque burden in promoting intimal hyperplasia after stent implantation. The aim of this study was to test the hypothesis that plaque removal with directional atherectomy before stent implantation may lower the intensity of late neointimal hyperplasia, reducing the incidence of in-stent restenosis. METHODS AND RESULTS: Seventy-one patients with 90 lesions underwent directional atherectomy before coronary stenting. Intravascular ultrasound-guided stenting was performed in 73 lesions (81%). Clinical success was achieved in 96% of patients. Procedural complications were as follows: emergency bypass surgery in 1 patient (1.4%), who died 2 weeks later; Q-wave myocardial infarction in 2 patients (2.8%); and non-Q-wave myocardial infarction in 8 patients (11.3%). None of the patients had stent thrombosis at follow-up. Angiographic follow-up was performed in 89% of eligible patients at 5.7+/-1.7 months. Loss index was 0.33 (95% CI, 0.26 to 0.40), and angiographic restenosis was 11% (95% CI, 5% to 20%). Clinical follow-up was performed in all patients at 18+/-3 months. Target lesion revascularization was 7% (95% CI, 3% to 14%). CONCLUSIONS: Directional atherectomy followed by coronary stenting could be performed with good clinical success rate. Also, these data point to a possible reduction in angiographic restenosis and a significant reduction in the need for repeated coronary interventions. Therefore, a randomized clinical trial seems appropriate to test the validity of this approach.

Aged↗

Comparison of angiographic and clinical outcomes of coronary stenting of chronic total occlusions versus subtotal occlusions.

The objective of this study was to assess the short- and long-term outcome of patients undergoing coronary stenting for chronic total occlusions compared with a control patient population with nonocclusive stenoses. A total of 789 consecutive patients (1,043 lesions) underwent coronary stenting using a high-pressure stent optimization technique. The study population was divided into total occlusion group (94 consecutive patients [95 lesions] with chronic total occlusions) and subtotal occlusion group (695 consecutive patients [948 lesions] with nonocclusive stenoses). There was no difference in post-procedure angiographic minimum lumen diameter (3.13 +/- 0.48 vs 3.15 +/- 0.57 mm, p = 0.72) and minimum intrastent cross-sectional area by intravascular ultrasound (7.31 +/- 2.06 vs 7.64 +/- 2.53 mm2, p = 0.26) between the total and subtotal groups, respectively. Subacute thrombosis occurred in 2 patients (2.1%) in the total group compared with 9 patients (1.3%) in the subtotal group (p = 0.63). Angiographic restenosis occurred in 27% vs 22% (p = 0.40) and repeat angioplasty in 15% vs 13% (p = 0.62) in the total and subtotal groups, respectively. Thus, coronary stenting of chronic total occlusions after successful recanalization could be performed with a high success rate. In addition, the incidence of stent thrombosis, angiographic restenosis, and the need for target lesion revascularization is comparable to that of an unselected cohort of patients with nonocclusive stenoses.

Aged↗

Laser wire for crossing chronic total occlusions: "learning phase" results from the U.S. TOTAL trial. Total Occlusion Trial With Angioplasty by Using a Laser Wire.

The Prima laser guidewire system (Spectranectics Corp., Colorado Springs, CO) consists of an 0.018" hypotube containing a bundle of 45-microm optical fibers coupled to a pulsed excimer laser operating at a tip fluence of 60 ml/mm2 and a repetition rate ranging from 25-40 Hz. This laser guidewire was specifically designed to cross total occlusions refractory to passage with conventional wires. The Prima wire was evaluated in a feasibility study at 15 U.S. centers. Following failure to cross a total occlusion with approved guidewires, the Prima wire was utilized in 179 patients. Average age of subjects was 61 yr. Lesion locations included left anterior descending (36%), right (45%), and circumflex (19%) coronary arteries. Mean angiographic age of total occlusions was 70 wk (range, 2-1,020 wk, median, 14 wk). The use of the Prima wire either solely or in combination with conventional guidewires resulted in successful crossing in 61% of these previously impenetrable occlusions. Failure of the device was commonly related to length of the occlusion and tortuosity along the occluded pathway. Major complications included myocardial infarction in 7 patients (3.9%), tamponade in 3 (1.7%), and death in 2 (1.1%). This "learning phase" pilot study confirmed the feasibility of a laser guidewire in chronic total occlusions that are resistant to passage of conventional guidewires. An extended registry at these investigative sites is planned.

Adult↗