Acute toxicity of diazinon to the amphipod, Gammarus pseudolimnaeus: implications for water quality criteria development.
Explore the source record for details and available documents.
Amphipoda↗
Biomedical subjects
R D Anderson
Publications and source records attributed to R D Anderson.
Design of the therapeutic angiogenesis with recombinant fibroblast growth factor-2 for intermittent claudication (TRAFFIC) trial.
The Therapeutic Angiogenesis With Recombinant Fibroblast Growth Factor-2 for Intermittent Claudication (TRAFFIC) is a large, randomized, placebo-controlled, regimen-finding trial of intra-arterial recombinant fibroblast growth factor-2 in patients with intermittent claudication. This report describes the major design considerations and end points in TRAFFIC.
Double-Blind Method↗
Syphilitic aortitis.
A case of syphilitic aortitis, complicated by bilateral coronary ostial stenosis, in a 40-year-old man is described. Treatment included coronary artery bypass grafting and a drug regimen of penicillin. At 3-month follow-up, an exercise stress test revealed no signs of ischemia.
Adult↗
Does the presence of thrombus seen on a coronary angiogram affect the outcome after percutaneous coronary angioplasty? An Angiographic Trials Pool data experience.
OBJECTIVES: This study aimed to determine whether pre-existing angiographic thrombus was associated with adverse in-hospital and six-month outcomes after percutaneous coronary interventions. BACKGROUND: There are conflicting data about whether pre-existing thrombus is an independent predictor of adverse in-hospital and short-term outcome after coronary interventions. METHODS: The Angiographic Trials Pool, a data set derived from eight prospective randomized trials, was analyzed. The study population consisted of 7,917 patients who underwent coronary interventions between 1986 and 1995. Two trials were excluded because they did not collect information regarding thrombus. Patients from the other six trials were divided on the basis of the presence or absence of thrombus. RESULTS: In patients with (n = 2,752) and without (5,165) thrombus, in-hospital mortality following angioplasty was low (0.8 vs. 0.6%, p = 0.207). Several adverse outcomes were higher in patients with thrombus: death/myocardial infarction (8.4 vs. 5.5%, p < or = 0.001), in-hospital abrupt closure (5.9 vs. 3.9%, p < or = 0.001) and an in-hospital composite of death, myocardial infarction and/or repeat revascularization (15.4 vs. 11.2%, p < or = 0.001). Six-month mortality was low and comparable between the two groups (2.1 vs. 1.8%, p = 0.34), but the incidence of six-month death/myocardial infarction was higher in patients with thrombus (11.7 vs. 8.7%, p < or = 0.0001). CONCLUSIONS: Percutaneous coronary angioplasty can be performed with low mortality in patients with pre-existing thrombus, although these patients are at higher risk of in-hospital and six-month death/myocardial infarction. Continued efforts are required to optimize the outcome in these high risk patients.
Aged↗
Adenoviral-mediated transfer of the TNF-related apoptosis-inducing ligand/Apo-2 ligand gene induces tumor cell apoptosis.
TNF-related apoptosis-inducing ligand (TRAIL) is a member of the TNF superfamily of cytokines that induces apoptosis in a variety of cancer cells. The results presented in this study demonstrate that introduction of the human TRAIL gene into TRAIL-sensitive tumor cells using an adenoviral vector leads to the rapid production and expression of TRAIL protein, and subsequent death of the tumor cells. Tumor cell death was mediated by an apoptotic mechanism, as evidenced by the activation of caspase-8, cleavage of poly(ADP-ribose) polymerase, binding of annexin V, and inhibition by caspase inhibitor zVAD-fmk. These results define a novel method of using TRAIL as an antitumor therapeutic, and suggest the potential use for an adenovirus-encoding TRAIL as a method of gene therapy for numerous cancer types in vivo.
Adenoviruses, Human↗
A simple method for the rapid generation of recombinant adenovirus vectors.
Recombinant adenoviruses are useful vectors for basic research. When the vectors are used for delineating protein function, several viruses, each containing a mutated version of the transgene are compared at the same time. However, methods to generate multiple vectors simultaneously within a short time period are cumbersome. In this report, we show that a novel backbone plasmid, when cotransfected with routinely used shuttle vectors into HEK293 cells allowed for production of recombinant viruses in an average of 14 days. The recombinant viruses had no detectable wild-type virus contamination by A549 plaque assay and only three to 300 E1a copies per 109 adenovirus genomes by a sensitive PCR-based assay. Further culturing or serial amplification did not result in wild-type revertants nor did cultures show increased levels of E1a copy number by quantitative PCR. Thus, recombinant adenovirus vectors can be produced very simply, rapidly and with little to no contaminating wild-type particles. This system should facilitate the generation of multiple genetic variants by eliminating the need for time-consuming plaque purification and the need to manipulate and screen very large plasmids. We call this the RAPAd.I system.
Adenoviridae↗
Lack of progress in cardiogenic shock: lessons from the GUSTO trials.
AIMS: We used the GUSTO-I and GUSTO-III databases to evaluate our performance in treating cardiogenic shock patients over much of the 1990s. METHODS AND RESULTS: GUSTO-I (1990-1993) and GUSTO-III (1995-1997) prospectively identified all patients with cardiogenic shock complicating acute myocardial infarction. Demographics, clinical presentation and outcomes for cardiogenic shock patients in the two trials were compared. Only patients enrolled with cardiogenic shock in countries common to both trials were included in these analysis. The 695 patients with cardiogenic shock in GUSTO-III were compared with the 2814 patients with cardiogenic shock in GUSTO-I. GUSTO-III patients were older (P=0.0001) and more likely to be diabetic (P=0.009) and hypertensive (P=0.025). They had a higher Killip class (P=0.002) and significantly greater index anterior infarction than cardiogenic shock patients enrolled in GUSTO-I. Time to treatment, presentation heart rate, and diastolic blood pressure were similar; however, systolic blood pressure at presentation was higher among GUSTO-III patients (P=0.002). Rates of coronary angiography, pulmonary artery catheterization, and mechanical ventilation declined in GUSTO-III compared with GUSTO-I (P=0.001); rates of angioplasty and bypass surgery were similar. Cardiogenic shock mortality in GUSTO-III was significantly higher than in GUSTO-I (62 vs 54%, P=0.001), as were rates of reinfarction (14 vs 11%, P=0.013) and recurrent ischaemia (35 vs 27%, P=0.00001). Mortality at non-U.S. sites (68 and 64%) was higher than at U.S. sites (53 and 50%) in both GUSTO-I and GUSTO-III studies, respectively. Angioplasty, bypass surgery, and balloon pump rates were lower for non-U.S. patients. CONCLUSIONS: Cardiogenic shock continues to be associated with high mortality in thrombolytic-treated patients. Lower mortality observed in the U.S.A. supports consideration for percutaneous and surgical revascularization.
Aged↗
Systemic hyperosmolality improves beta-glucuronidase distribution and pathology in murine MPS VII brain following intraventricular gene transfer.
Mucopolysaccharidosis VII, a classical lysosomal storage disease, is caused by deficiency of the enzyme beta-glucuronidase. Central nervous system (CNS) manifestations are severe with accumulations of storage vacuoles in all cell types. Intraventricular gene transfer can lead to transduction of the ependyma, with production and secretion of beta-glucuronidase into the cerebral spinal fluid and underlying cortex resulting in reversal of disease pathology restricted to the periventricular areas. We tested if systemic hyperosmolality would increase the distribution of beta-glucuronidase in brain parenchyma after intraventricular virus injection. Mice were administered mannitol, intraperitoneally, 20 days after gene transfer and 1 day prior to sacrifice. Mannitol-induced systemic hyperosmolality caused a marked penetration of beta-glucuronidase into the brain parenchyma. If mannitol was administered at the time of the intraventricular injection of virus, there was penetration of vector across the ependymal cell layer, with infection of cells in the subependymal region. This also resulted in increased beta-glucuronidase activity throughout the brain. Sections of brains from beta-glucuronidase-deficient mice showed correction of cellular pathology in the subependymal region plus cortical structures away from the ventricular wall. These data indicate that virus-mediated gene transfer to the brain via the ventricles, coupled with systemic mannitol administration, can lead to extensive CNS distribution of beta-glucuronidase with concomitant correction of the storage defect. Our findings have positive therapeutic implications for the treatment of CNS disorders with gene transfer vectors and recombinant proteins.
Adenoviridae↗
Extensive beta-glucuronidase activity in murine central nervous system after adenovirus-mediated gene transfer to brain.
Mucopolysaccharidosis type VII (MPS VII), caused by beta-glucuronidase deficiency, is a classic lysosomal storage disease. In the central nervous system (CNS), there is widespread pathology with distention of vacuoles in neurons and glia. An approach to therapy for MPS VII would require extensive delivery of enzyme to the CNS and subsequent uptake by the affected cells. In this study we show that intrastriatal injection of recombinant adenovirus encoding beta-glucuronidase (Ad betagluc) to MPS VII or wild-type mice results in focal, intense beta-glucuronidase mRNA expression near the injection site. Further, histochemical staining for enzyme activity showed that beta-glucuronidase activity extended well beyond transduced cells. Activity was detected throughout the ipsilateral striatum as well as in the corpus callosum, ventricles, and bilateral neocortex. Similarly, after injection into the right lateral ventricle or cisterna magna, enzyme activity was present in the ependymal cells of the ventricles, in the subarachnoid spaces, and also in the underlying cortex (150-500 microm from ependyma). The distribution of enzyme was most extensive 21 days after gene transfer to normal mouse brain, with more than 50% of the hemisphere positive for beta-glucuronidase activity. Eighty-four days after adenovirus injection a substantial level of enzyme expression remained (>40% of hemisphere positive for beta-glucuronidase activity). Histological sections from striatum of beta-glucuronidase-deficient mice injected with Ad betagluc showed a marked reduction in the number of distended vacuoles in both neurons and glia, as compared with uninjected striatum. Importantly, correction was noted in both hemispheres. Our finding that a relatively small number of transduced cells produce enzyme that reaches a large proportion of the CNS has favorable implications in developing direct gene transfer therapies for lysosomal storage disorders.
Adenoviridae↗
A single-dose study to assess the penetration of stavudine into human cerebrospinal fluid in adults.
Penetration of stavudine into the cerebrospinal fluid (CSF) was studied in healthy humans. In this open, randomized study, a single oral dose of 40 mg of stavudine was given to 12 fasting volunteers > or = 18 years of age. Subjects were divided into three groups based on the time of CSF sampling (i.e., 0.75-1.25, 2-3, or 4-5 hours after dosing). Blood samples were collected over an 8-hour period after dosing and included a sample simultaneous with CSF collection to permit an estimate of CSF : plasma ratios. Stavudine concentrations in plasma and CSF were determined by a validated high-performance liquid chromatography method. Repeated measurements of vital signs, physical examination, and clinical laboratory tests indicated that the stavudine dose was well tolerated. CSF levels were not detected 0.75 to 1.25 hours after dosing. Thereafter, levels were detected in the CSF of five subjects; the mean concentration was 61 ng/ml. The mean CSF: plasma ratio increased with time, from 0.16 at 2 to 3 hours postdose in one subject to 0.40 at 4 to 5 hours postdose in four subjects. In conclusion, the mean stavudine concentration of 61 ng/ml achieved in the CSF of five subjects exceeds the ED50 of clinical isolates of HIV (230 nM, 52 ng/ml).
Administration, Oral↗
Prognostic value of congestive heart failure history in patients undergoing percutaneous coronary interventions.
OBJECTIVES: We sought to determine the prognostic significance of a history of congestive heart failure above that provided by baseline ejection fraction in patients undergoing percutaneous coronary interventions. BACKGROUND: Left ventricular function is a known predictor of survival in patients with coronary artery disease, as is a history of congestive heart failure. The contribution of heart failure history independent of left ventricular function is unknown. METHODS: Data were pooled from four interventional trials and the Duke University database. The combined dataset included 5,260 patients undergoing percutaneous interventions, 334 with and 4,926 without a history of heart failure. Patients were defined by the treating physician as having a clinical history of heart failure at the time of enrollment. RESULTS: The 30-day and 6-month mortality were higher in patients with a clinical history of congestive heart failure than in those without such a history (2% vs. <1%, p=0.002 at 30 days, 5% vs. 1%, p=0.001 at 6 months). Heart failure history did not influence the incidence of myocardial infarction, use of angioplasty or the use of bypass surgery during follow-up. Multivariable analysis revealed that heart failure history added significantly to ejection fraction in predicting intermediate-term (6-month) mortality (p=0.01). Stepwise logistic regression also revealed heart failure history to be an independent predictor of 6-month mortality (odds risk 1.9, 95% confidence interval 1.1 to 3.5). CONCLUSIONS: A clinical history of congestive heart failure is associated with increased early and intermediate-term mortality in patients undergoing percutaneous revascularization. Congestive heart failure history appears to provide prognostic information independent of that available from a patient's left ventricular function. These findings suggest that patients with a clinical history of congestive heart failure who undergo a percutaneous intervention should be closely monitored, especially those with the lowest ejection fractions.
Aged↗
Functional rescue of the sarcoglycan complex in the BIO 14.6 hamster using delta-sarcoglycan gene transfer.
Four types of limb-girdle muscular dystrophy (LGMD) are known to be caused by mutations in distinct sarcoglycan genes. The BIO 14.6 hamster is a model for sarcoglycan-deficient LGMD with a deletion in the delta-sarcoglycan (delta-SG) gene. We investigated the function of the sarcoglycan complex and the feasibility of sarcoglycan gene transfer for LGMD using a recombinant delta-SG adenovirus in the BIO 14.6 hamster. We demonstrate extensive long-term expression of delta-sarcoglycan and rescue of the entire sarcoglycan complex, as well as restored stable association of alpha-dystroglycan with the sarcolemma. Importantly, muscle fibers expressing delta-sarcoglycan lack morphological markers of muscular dystrophy and exhibit restored plasma membrane integrity. In summary, the sarcoglycan complex is requisite for the maintenance of sarcolemmal integrity, and primary mutations in individual sarcoglycan components can be corrected in vivo.
Adenoviridae↗
Endoscopic malar/midface suspension procedure.
Aging in the midface area is seen with ptosis of the malar tissues, hollowing of the infraorbital area, deepening of the nasolabial and mandibular labial folds, and increased jowling. Some of these aging changes are usually not corrected by a standard SMAS face lift. An endoscope-dependent technique was created specifically to address the midface area. The midface tissues are elevated and released in a subperiosteal manner and then suspended to a higher position after endoscopic dissection of the temporal area. The tissues are repositioned to a higher position on the malar area with softening of the nasolabial fold, decreased jowls, and recreation of the desired youthful fullness in the malar and infraorbital area. This procedure can be combined easily with other facial procedures such as rhytidectomy, neck lift, temple lift, and laser resurfacing when indicated. More than 200 procedures have been completed in the last 22 months. This report presents the surgical technique with early follow-up results.
Endoscopy↗
Ongoing open-label trials of triple therapy with stavudine and lamivudine or stavudine and didanosine plus nelfinavir.
The VZN and ZEN studies are non-comparative trials assessing triple combination therapy comprising thymidine and non-thymidine analogue nucleoside reverse transcriptase inhibitors plus a protease inhibitor. Preliminary data are available for the VZN study and recruitment for the ZEN study is underway.
Adult↗
Relationship between diabetes mellitus and long-term survival after coronary bypass and angioplasty.
BACKGROUND: Recent subgroup analyses of randomized trials have suggested that percutaneous intervention in diabetic patients with multivessel disease results in higher mortality than coronary artery bypass graft surgery (CABG). We studied the relationship between diabetes and survival after revascularization in a large prospective cohort of patients with multivessel coronary artery disease. METHODS AND RESULTS: By analyzing data for 3220 patients (24% diabetic) with symptomatic two- or three-vessel coronary disease who were undergoing percutaneous transluminal coronary angioplasty (PTCA) or CABG at Duke University Medical Center between 1984 and 1990, we found that at 5 years, unadjusted survival in the group of patients undergoing CABG was 74% in diabetics and 86% in nondiabetics. Similarly, 5-year survival among PTCA patients was 76% in diabetics and 88% in patients without diabetes. After adjustment for baseline characteristics, diabetic patients receiving either PTCA or CABG had significantly poorer survival than nondiabetics (chi2=43.56, P<.0001). Unlike previous studies, however, there was no significant differential effect of diabetes on outcome between patients treated with PTCA and those treated with CABG (chi2=0.01, P=.91). CONCLUSIONS: Although diabetes was associated with a worse long-term outcome after both PTCA and CABG in patients with multivessel coronary artery disease, the effect of diabetes on prognosis was similar in both treatment groups. Thus, our findings support the concept that the choice of initial revascularization strategy should not be based exclusively on a history of diabetes but rather should rely on other factors, such as angiographic suitability and clinical status.
Aged↗
New concept in coronary angioplasty: dilatation with a helical balloon that allows simultaneous autoperfusion.
These preclinical studies investigate a new concept in coronary angioplasty and balloon catheter technology (the P100 catheter). The study sought to evaluate the morphology of experimental coronary arterial plaques dilated with the P100 in comparison to standard balloons, to determine the in vitro flow rates occurring during the inflation of the P100 in comparison to available perfusion catheters, and to assess the in vivo coronary flow velocity and the presence of ischemia during prolonged inflations with the P100. The development of myocardial ischemia is a major limitation of standard balloon angioplasty. To limit ischemia, autoperfusion catheters have been developed, in which blood flows through the balloon in the central catheter shaft. However, as the flow lumen profile is reduced to enhance the performance of these devices, so is the accompanying flow. An angioplasty catheter was designed to evaluate the feasibility of continuous autoperfusion around the dilatation balloon. The balloon surface was engineered to develop a helical trough for blood flow to occur during inflation. Arterial plaque morphology following angioplasty with the P100 (n = 8) and with standard balloons (n = 8) was evaluated in a swine model. In vitro flow rates during inflation of the P100 and available perfusion catheters were determined using 33% glycerol solution. In vivo coronary flow velocity was determined with a Doppler-tipped wire during 60-min continuous inflations with the P100, and 15-sec inflations with a standard balloon in 12 vessel segments in 7 dogs; using 3.0-3.5-mm-diameter balloons. All lesions were successfully dilated (< 50% luminal diameter stenosis) with the P100 and standard balloons. There were no morphologic differences in plaques dilated with P100 compared to standard balloons. In vitro flow rates with conventional 3.0-mm balloon perfusion catheters ranged from 27.1 +/- 2.1 ml/min (RX Flowtrack) to 38.7 +/- 0.9 ml/min (Stack Perfusion), P < .05. Flow with the P100 ranged from 54.8 +/- 4.3 ml/min (2.5-mm balloon) to 103.2 +/- 4.5 ml/min (3.5-mm balloon), P < .05. Distal average peak coronary flow velocity during prolonged P100 inflations varied from 69 +/- 7% of baseline at 5 min to 83 +/- 8% of baseline at 40 min, with an upward trend in velocity the longer the balloon was inflated. Hemodynamics remained stable. Experimental plaques are successfully dilated with a helical balloon by a mechanism that appears similar to the dilatation mechanism of standard balloons. These preclinical studies show that angioplasty and autoperfusion can be accomplished by a balloon that does not have complete surface area contact with the vessel wall. A gap created by the helix can thus provide a conduit for blood flow. Clinical studies will determine whether this innovation, which alters the tubular geometry of current angioplasty balloons, will provide autoperfusion and equivalent dilatation effects in human.
Analysis of Variance↗
Coronary artery angioplasty with a helical autoperfusion balloon catheter.
The initial in-hospital and long-term clinical experience with a helical autoperfusion balloon catheter in the treatment of coronary artery disease is reported. This new catheter design allows blood to flow passively around the inflated balloon through a protected helical channel molded into the balloon surface. Twelve consecutive patients underwent PTCA. Continuous ST monitoring, heart rate, average peak distal coronary blood flow velocity (APV), coronary blood flow (CBF), dP/dt and systemic and pulmonary arterial pressures were determined during PTCA. During balloon inflation there were no hemodynamic changes, TIMI flow was 1.7 +/- 0.8, and APV was 39% of baseline. Luminal diameter stenosis improved from 61 +/- 17 to 29 +/- 13% (P < 0.05) following PTCA. Mean continuous inflation duration was 385 +/- 215 sec and 6/12 patients had > or = 7.5-min inflations. There were no in-hospital adverse cardiac events. One patient developed recurrent angina during 8 mo of follow-up and underwent successful PTCA of a restenotic lesion. We conclude that human plaques can be successfully dilated with a helical balloon catheter that provides autoperfusion and the ability to perform prolonged inflations with hemodynamic stability. A comparison of this PTCA catheter with standard balloon catheters is warranted.
Adult↗
Use of intraaortic balloon counterpulsation in patients presenting with cardiogenic shock: observations from the GUSTO-I Study. Global Utilization of Streptokinase and TPA for Occluded Coronary Arteries.
OBJECTIVES: We sought to examine the use, complications and outcomes with early intraaortic balloon counterpulsation (IABP) in patients presenting with cardiogenic shock complicating acute myocardial infarction and treated with thrombolytic therapy. BACKGROUND: The use of IABP in patients with cardiogenic shock is widely accepted; however, there is a paucity of information on the use of this technique in patients with cardiogenic shock who are treated with thrombolytic therapy. METHODS: Patients who presented within 6 h of chest pain onset were randomized to one of four thrombolytic regimens. Cardiogenic shock was not an exclusion criterion, and data for these patients were prospectively collected. Patients presenting with shock were classified into early IABP (insertion within one calendar day of enrollment) or no IABP (insertion on or after day 2 or never). RESULTS: There were 68 (22%) IABP placements in 310 patients presenting with shock. Early IABP use occurred in 62 patients (20%) and none in 248 (80%). Most IABP use occurred in the United States (59 of 68 IABP placements) involving 32% of U.S. patients presenting with shock. Despite more adverse events in the early IABP group and more episodes of moderate bleeding, this cohort showed a trend toward lower 30-day and 1-year mortality rates. CONCLUSIONS: IABP appears to be underutilized in patients presenting with cardiogenic shock, both within and outside the United States. Early IABP institution is associated with an increased risk of bleeding and adverse events but a trend toward lower 30-day and 1-year all-cause mortality.
Aged↗