Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.1.1.6 (CAD)
 4,420 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The role of adjuvant radiation therapy (RT) in the management of advanced-stage Hodgkin's disease (HD) was analyzed in 222 patients who attained a complete remission (CR) with alternating chemotherapy combinations. Mechlorethamine, vincristine, procarbazine, and prednisone/doxorubicin, bleomycin, vinblastine, and dacarbazine (MOPP/ABVD) or MOPP/ABV alternating with the lomustine, melphalan, and vindesine combination (MOPP/ABV/CAD) were similarly effective in inducing a CR in 222 of 270 (83%) patients. These patients were scheduled to receive consolidative RT to bulky disease or other critical sites of initial nodal involvement to a total dose of 2,000 cGy, with an optional additional boost of 1,000 cGy. However, only 125 (56%) patients received radiation to all initial nodal sites of disease. In 69 (31%) patients, only selected nodal sites were included in the radiation fields, and 28 (13%) did not receive any RT. Of the 222 CR patients, 42 (19%) relapsed during a median follow-up period of 6.5 years (range, 2 to 15 years). Of these, 26 (62%) patients relapsed exclusively in unirradiated nodal sites, six (14%) within irradiated sites, and 10 (24%) both within and outside irradiated fields. The actuarial 10-year relapse-free survival (RFS) and overall survival (OS) for patients receiving radiation to all initially involved nodal sites were 89% and 94%, respectively, compared with 68% and 71% (P less than .0001) for patients who had only partial or no RT. Cox proportional hazards regression analysis showed that RT to all sites of initial disease was the most significant independent covariate (P less than .005) affecting RFS and OS. These data demonstrate that residual microscopic disease is relatively frequent in patients with apparent CR after alternating combination chemotherapy, and that irradiation of all sites of initial nodal involvement decreases relapse and improves survival in advanced-stage HD.
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PMID:Impact of adjuvant radiation on the patterns and rate of relapse in advanced-stage Hodgkin's disease treated with alternating chemotherapy combinations. 196 May 60

Vindesine (desacetyl vinblastine amide sulfate, DVA) was used in combination with CCNU (lomustine) and melphalan (Alkeran) (CAD) to treat 15 heavily pretreated patients with Hodgkin's disease in relapse. The patients were treated with up to six cycles, depending upon their response. Two patients (13%) achieved a complete remission (CR) and five (33%) patients a partial remission (PR). The major toxicity was prolonged thrombocytopenia, which was decreased by a reduction in the initial drug doses for patients who had received extensive prior chemotherapy and radiotherapy (RT). The CAD regimen was then alternated with nitrogen mustard or cyclophosphamide, vincristine, procarbazine, and prednisone (MOPP, C-MOPP) and doxorubicin (Adriamycin), bleomycin, and vinblastine (ABV) for a total of nine cycles in 25 patients with Hodgkin's disease in relapse with somewhat more favorable prognostic features. Two patients also received low-dose RT to areas of bulky nodal disease. Eleven patients (44%) achieved a CR and seven (28%) a PR. Of the 11 CR patients, six remain in remission. The serious toxicity was comparable to that seen with other combination chemotherapy regimens. These results indicated that the CAD/MOPP/ABVD regimen is as active as other so-called 'salvage' regimens for Hodgkin's disease in relapse, and suggest that it might be useful for newly diagnosed Hodgkin's disease.
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PMID:Combination chemotherapy for the treatment of Hodgkin's disease in relapse. Results with lomustine (CCNU), melphalan (Alkeran), and vindesine (DVA) alone (CAD) and in alternation with MOPP and doxorubicin (Adriamycin), bleomycin, and vinblastine (ABV). 619 13

Our purpose was to assess the efficacy and safety of intravenous ATP for the acute termination of paroxysmal supraventricular tachycardia. There were 14 women and 10 men, aged 38 +/- 15 years. Three patients had evidence of structural heart disease (Ebstein's anomaly associated to atrial septal defect, operated mitral stenosis with insertion of a mechanical heart valve and CAD respectively). Twelve patients had Wolff-Parkinson-White syndrome and another had undergone surgical ablation of an accessory pathway. At the time of electrophysiologic testing, ATP was administered during episodes of paroxysmal supraventricular tachycardia, via a central vein, in incremental doses of 5, 10 and 20 mg followed by a flush of 10 c.c. of isotonic saline. The mechanism of the arrhythmia was orthodromic AV reentrant tachycardia in 19 (79%), AV nodal reentrant tachycardia in 4 (16.6%) and atrial tachycardia in one patient. The mean frequency of the tachycardia was 174 +/- 33 b.p.m. A dose of 5 mg was effective in 16 patients (66%), 5 required 10 mg and two required 20 mg for termination of the tachycardia. In the patient with atrial tachycardia ATP was not effective. The average time after injection to termination of the arrhythmia was 16 +/- 8 seconds. Orthodromic AV reentrant tachycardia was interrupted in the AV node limb in all but one patient and AV nodal reentry was terminated in the "slow-pathway" in three of the four patients. Nine patients had premature ventricular complexes, isolated or in couplets, after the termination of the SVT. Three patients had immediate recurrence of the SVT.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Efficacy and safety of adenosine triphosphate in the control of supraventricular paroxysmal tachycardia]. 804 86

Symptomatic bradyarrhythmia occurs most often in aged patients. Most of these patients have multiple coronary risk factors and present with angina-like symptoms. The coexistence of CAD not only has major effects on their prognosis but also influences the long-term care. This study was designed to evaluate the incidence of coexistent CAD in patients with symptomatic bradyarrhythmias and its relationship to conventional coronary risk factors in Chinese people. From May 1996 to April 1998, we prospectively studied all consecutive patients admitted to our institution for symptomatic bradyarrhythmias requiring permanent pacemaker implantation. Coronary angiographies were performed non-selectively at the same session of pacemaker implantation. Based on the presence or absence of CAD, patients were divided into two groups for analysis. Multivariate logistic regression analysis was performed to determine independent predictors of CAD including sex, age, diabetes mellitus (DM), hypertension, hypercholesterolemia, and smoking. The odds-ratio (OR) and 95% confidence interval (CI) were determined. A total of 113 patients [68 males and 45 females, mean age 70.4+/-8.2 years old (range 45-86)] were included in our study. The diagnosis was sick sinus syndrome in 69 patients (61%) and atrioventricular block in 44 patients (39%). The incidence of CAD based on coronary angiography was 20%. The nodal-related artery was seldom involved among patients with coexistent CAD and symptomatic bradyarrhythmias (9%), and most patients had significant stenosis over LAD (74%). The baseline characteristics and presenting symptoms were not different statistically between patients with or without CAD. Hypercholesterolemia (OR 6.6, 95% CI 2.0-22.2, p=0.002) and DM (OR 4.7, 95% CI 1.3-17.2, p=0.020) were the two most significant independent predictors of CAD. In our patients with symptomatic bradyarrhythmias requiring permanent cardiac pacing, the incidence of CAD was 20% as determined by coronary angiography (CAG). Hypercholesterolemia and DM were the two most significant independent predictors for CAD in these patients. The nodal artery was seldom involved in patients with coexistent CAD and symptomatic bradyarrhythmias.
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PMID:The incidence of coronary artery disease in patients with symptomatic bradyarrhythmias. 1169 78

The management of prostate cancer patients with a significant risk of pelvic lymph node involvement is controversial. Both whole pelvis radiotherapy and dose escalation to the prostate have been linked to improved outcome in such patients, but it is unclear whether conventional whole pelvis doses of only 45-50 Gy are optimal for ultimate nodal control. The purpose of this study is to examine the dosimetric and clinical feasibility of combining prostate dose escalation via hypofractionation with conformal avoidance-based IMRT (H-CAD) dose escalation to the pelvic lymph nodes. One conformal avoidance and one conventional plan were generated for each of eight patients. Conformal avoidance-based IMRT plans were generated that specifically excluded bowel, rectum, and bladder. The prostate and lower seminal vesicles (PTV 70) were planned to receive 70 Gy in 2.5 Gy/fraction while the pelvic lymph nodes (PTV 56) were to concurrently receive 56 Gy in 2 Gy/fraction. The volume of small bowel receiving >or=45 Gy was restricted to 300 ml or less. These conformal avoidance plans were delivered using helical tomotherapy or LINAC-based IMRT with daily imaging localization. All patients received neoadjuvant and concurrent androgen deprivation with a planned total of two years. The conventional, sequential plans created for comparison purposes for all patients consisted of a conventional 4-field pelvic box prescribed to 50.4 Gy (1.8 Gy/fraction) followed by an IMRT boost to the prostate of 25.2 Gy (1.8 Gy/fraction) yielding a final prostate dose of 75.6 Gy. For all plans, the prescription dose was to cover the target structure. Equivalent uniform dose (EUD) analyses were performed on all targets and dose-volume histograms (DVH) were displayed in terms of both physical and normalized total dose (NTD), i.e. dose in 2 Gy fraction equivalents. H-CAD IMRT plans were created for and delivered to all eight patients. Analysis of the H-CAD plans demonstrates prescription dose coverage of >95% of both the PTV 70 (prostate) and PTV 56 (nodes). The EUDs for PTV 70 and PTV 56 were greater than prescription dose for all eight plans. Analysis of bio-effective DVHs demonstrated similar amounts of small bowel receiving >or=45 Gy for H-CAD and sequential plans, in spite of the significantly higher dose to which H-CAD treated the pelvic nodes. The treatment was well tolerated in the eight treated patients in that no grade 2 or higher acute gastrointestinal toxicities were seen. Prostate hypofractionation with concurrent conformal avoidance-based pelvic IMRT for high risk prostate cancer represents an efficient and promising method for achieving dose escalation both of pelvic lymph nodes and the prostate with modest acute toxicity. Unlike a vascular-guided targeting approach, conformal avoidance has the potential advantage of also encompassing at-risk nodes that are not contained within major nodal chains. A phase II trial to more thoroughly examine this treatment approach is currently underway.
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PMID:Pelvic nodal dose escalation with prostate hypofractionation using conformal avoidance defined (H-CAD) intensity modulated radiation therapy. 1693 15

The Xyleborina ambrosia beetle genus Xylosandrus contains 54 species, several of which are of economic importance. The monophyly of the genus was tested using a data set comprised of multiple gene loci: 28S rDNA; the mitochondrial gene cytochrome oxidase I (COI); and the nuclear genes arginine kinase (ArgK), rudimentary (CAD), and Elongation Factor 1alpha (EF-1alpha). The nuclear protein-coding genes CAD and ArgK were used for the first time in phylogenetics of Scolytinae. Analyses were performed using Parsimony and Bayesian optimality criteria. Our analyses included 43 specimens representing 15 Xylosandrus species and 20 species from Amasa, Anisandrus, Cnestus, Euwallacea and Xyleborus, and two species from the outgroup genus Coccotrypes. All analyses recovered a polyphyletic Xylosandrus. Several species of Xylosandrus were consistently placed in clades with the genera Anisandrus and Cnestus with high support values (100% bootstrap support). Among these, was the economically important invasive species X. mutilatus, which was consistently recovered as part of the "Cnestus" clade. In our analyses, both CAD and ArgK demonstrated phylogenetic utility across varying nodal depths. Despite the selection of genes with signals at complementary phylogenetic depths, the data set used herein did not resolve the phylogeny of Xylosandrus and related genera. Since the taxon sample available for molecular work represents only a fraction of Xylosandrus species, a complete revision that combines molecular and morphological data in a total evidence approach is recommended for the genus.
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PMID:Polyphyly of Xylosandrus Reitter inferred from nuclear and mitochondrial genes (Coleoptera: Curculionidae: Scolytinae). 1992 73

Computational modeling offers versatility, scalability, and cost advantages to researchers in the trauma and injury biomechanics communities. The Global Human Body Models Consortium (GHBMC) is a group of government, industry, and academic researchers developing human body models (HBMs) that aim to become the standard tool to meet this growing research need. The objective of this study is to present the methods used to develop the average seated male occupant model (M50, weight = 78 kg, height = 175 cm) from five separately validated body region models (BRMs). BRMs include the head, neck, thorax, abdomen, and a combined pelvis and lower extremity model. Modeling domains were split at the atlanto-occipital joint, C7-T1 boundary, diaphragm, abdominal cavity (peritoneum/retroperitoneum), and the acetabulum respectively. BRM meshes are based on a custom CAD model of the seated male built from a multi-modality imaging protocol of a volunteer subject found in literature.[1] Various meshing techniques were used to integrate the full body model (FBM) including 1-D beam and discrete element connections (e.g. ligamentous structures), 2D shell nodal connections (e.g. inferior vena cava to right atrium), 3D hexahedral nodal connections (e.g. soft tissue envelope connections between regions), and contact definitions varying from tied (muscle insertions) to sliding (liver and diaphragm contact). The model was developed in a general-purpose finite element code, LS-Dyna (LTSC, Livermore, CA) R4.2.1., and consists of 1.95 million elements and 1.3 million nodes. The element breakdown by type is 41% hexahedral, 33.7% tetrahedral, 19.5% quad shells and 5% tria shell. The integration methodology presented highlights the viability of using a collaborative development paradigm for the construction of HBMs, and will be used as template for expanding the suite of GHBMC models.
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PMID:A paradigm for human body finite element model integration from a set of regional models. 2284 15

Long-range signaling by morphogens and their inhibitors define embryonic patterning yet quantitative data and models are rare, especially in humans. Here, we use a human embryonic stem cell micropattern system to model formation of the primitive streak (PS) by WNT. In the pluripotent state, E-cadherin (E-CAD) transduces boundary forces to focus WNT signaling to the colony border. Following application of WNT ligand, E-CAD mediates a front or wave of epithelial-to-mesenchymal (EMT) conversion analogous to PS extension in an embryo. By knocking out the secreted WNT inhibitors active in our system, we show that DKK1 alone controls the extent and duration of patterning. The NODAL inhibitor cerberus 1 acts downstream of WNT to refine the endoderm versus mesoderm fate choice. Our EMT wave is a generic property of a bistable system with diffusion and we present a single quantitative model that describes both the wave and our knockout data.
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PMID:A wave of WNT signaling balanced by secreted inhibitors controls primitive streak formation in micropattern colonies of human embryonic stem cells. 3081 17