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J L Anderson

Publications and source records attributed to J L Anderson.

At least 73 records · Page 4Linked to original sources
PubMed1998

Multivariate associates of QT dispersion in patients with acute myocardial infarction: primacy of patency status of the infarct-related artery. TEAM-3 Investigators. Third trial of Thrombolysis with Eminase in Acute Myocardial Infarction.

BACKGROUND: QT dispersion (QTd; QT interval maximum minus minimum) has been shown to reflect regional variations in ventricular repolarization and is increased in patients with life-threatening ventricular arrhythmias. METHODS: To determine correlates of QTd in patients who had had myocardial infarction (MI), 207 patients (158 men, aged 57 +/- 11 years) with acute MI who were treated with alteplase or anistreplase within 2.7 +/- 0.9 hours of symptom onset were studied. Angiograms at a median of 27 hours after thrombolysis showed reperfusion (Thrombolysis in Myocardial Infarction grade > or =2) in 184 (88%) patients. QT was measured in 10 +/- 2 leads on discharge electrocardiograms with a computerized analysis program interfaced with a digitizer. Associations of QTd with 24 variables related to patient characteristics, acute MI, angiography, interventions, and radionuclide ventriculography were evaluated by univariate and multivariate regression. RESULTS: Univariate associations with QTd (p < or = 0.10) were Thrombolysis in Myocardial Infarction flow grade 0/1 versus 2/3 (QTd = 75 +/- 33 msec vs 53 +/- 22 msec, p < 0.0001), minimal luminal diameter (p = 0.007), left ventricular ejection fraction at discharge (p = 0.007), reinfarction (p = 0.01), number of leads with ST elevation (p = 0.05), end-systolic volume at discharge (p = 0.04), time to peak creatine kinase (p = 0.06), and YST elevation (p = 0.10). Independent associates of QTd were Thrombolysis in Myocardial Infarction grade 0/1 versus 2/3 (p < 0.0001), reinfarction (p = 0.005), and ejection fraction (p = 0.02). CONCLUSIONS: Successful thrombolysis is associated with less QTd in patients after acute MI. Our results support the hypothesis that QTd after MI depends on reperfusion status, reinfarction, and left ventricular function. Reduction in QTd may be an additional mechanism by which the benefit of thrombolytic therapy is realized.

Anistreplase↗
PubMed1998

Implementation of a computerized cardiovascular information system in a private hospital setting.

BACKGROUND: The use of clinical databases improves quality of care, reduces operating costs, helps secure managed care contracts, and assists in clinical research. Because of the large physician input required to maintain these systems, private institutions have often found them difficult to implement. At LDS Hospital in Salt Lake City, Utah, we developed a cardiovascular information system (LDS-CIS) patterned after the Duke University Cardiovascular Database and designed for ease of use in a private hospital setting. METHODS: Features of the LDS-CIS include concise single-page report forms, a relational database engine that is easily queried, automatic generation of final procedure reports, and merging of all data with the hospital's existing information system. So far, data from more than 14,000 patients have been entered. RESULTS: LDS-CIS provides access to data for research to improve patient care. For example, by using data generated by LDS-CIS, the policy requiring surgical backup during percutaneous transluminal coronary angioplasty was eliminated, resulting in no increased patient risk while saving nearly $1 million in 1 year. LDS-CIS generates physician feedback reports documenting performance compared with peers. This physician self-evaluation has standardized and improved care. Information from LDS-CIS has been instrumental in securing and maintaining managed care contracts. LDS-CIS risk analysis provides physicians with outcomes data specific to their current patient's demographics and level of disease to assist in point of care decisions. CONCLUSION: The use of LDS-CIS in the routine operations of LDS Hospital heart services has been found to be feasible, beneficial, and cost-effective.

Cardiac Catheterization↗
PubMed1998

Heart rate changes preceding ventricular ectopy in patients with ventricular tachycardia caused by reentry, triggered activity, and automaticity.

OBJECTIVES: Although enhanced sympathetic tone is thought to be proarrhythmic and beta-blockade reduces the risk of sudden cardiac death in survivors of myocardial infarction, the role of the autonomic nervous system in triggering spontaneous ventricular ectopy and ventricular tachycardia (VT) has not been fully elucidated. The purpose of this study was to compare and contrast autonomic tone preceding spontaneous ventricular arrhythmias in patients with reentrant, triggered, and automatic forms of VT. BACKGROUND: The prevailing model of reentrant VT is based on a triggering beat interacting with a fixed substrate. Within this model, cyclic fluctuations in autonomic tone comprise a "third factor" that may initiate the triggering extrasystoles as well as alter the substrate, facilitating perpetuation of tachycardia. Consistent with this model, adrenergic stimulation can facilitate the induction of reentrant arrhythmias as well as arrhythmias resulting from enhanced automaticity and those caused by triggered activity resulting from cyclic adenosine monophosphate-dependent delayed afterdepolarizations. METHODS AND RESULTS: On the basis of the results at electrophysiologic study, 26 patients with coronary artery disease were identified as having reentrant VT, 11 were identified as having idiopathic VT caused by triggered activity, and 4 were identified as having idiopathic VT caused by enhanced automaticity. Each patient underwent 24-hour electrocardiographic monitoring, and the mean sinus R-R intervals immediately preceding each sinus beat as well as the 15 beats preceding sinus beats, premature ventricular contractions (VPCs), and complex ventricular ectopy (couplet/non-sustained VT) were computed. In addition, high-frequency heart rate variability was determined. Heart rate accelerated before spontaneous ventricular ectopy for all three arrhythmia mechanisms. R-R intervals preceding episodes of complex ventricular ectopy were significantly shorter than the corresponding intervals preceding single VPCs in patients with 'riggered VT [p=0.006 and 0.01, R-R(-1) and R-R(-15), respectively] and in those with reentrant VT (p=0.007 and p=0.05). There were no corresponding differences in high-frequency heart rate variability. R-R intervals preceding single VPCs were significantly shorter than the corresponding intervals preceding sinus beats in patients with automatic VT (p=0.0004 and 0.0001, respectively), which was accompanied by a small reduction in high-frequency heart rate variability (p=0.04). CONCLUSIONS: Heart rate accelerates before spontaneous ventricular ectopy in patients with VT. The acceleration is disproportionate to parasympathetic withdrawal, implicating increased endogenous sympathetic tone in the genesis of spontaneous ventricular arrhythmias caused by all three electrophysiologic mechanisms: reentry, triggered activity, and automaticity.

Adolescent↗
PubMed1998

Genetic regulation of Dermatophagoides pteronyssinus-specific IgE responsiveness: a genome-wide multipoint linkage analysis in families recruited through 2 asthmatic sibs. Collaborative Study on the Genetics of Asthma (CSGA).

BACKGROUND: Dermatophagoides pteronyssinus (Der p) is one of the most frequently implicated allergens in atopic diseases. Although HLA could play an important role in the development of the IgE response to the Der p allergens, genetic regulation by non-HLA genes influences certain HLA-associated IgE responses to complex allergens. OBJECTIVE: To clarify genetic control for the expression of Der p-specific IgE responsiveness, we conducted a genome-wide search for genes influencing Der p-specific IgE antibody levels by using 45 Caucasian and 53 African American families ascertained as part of the Collaborative Study on the Genetics of Asthma (CSGA). METHODS: Specific IgE antibody levels to the Der p crude allergen and to the purified allergens Der p 1 and Der p 2 were measured. Multipoint, nonparametric linkage analysis of 370 polymorphic markers was performed with the GENEHUNTER program. RESULTS: The best evidence of genes controlling specific IgE response to Der p was obtained in 2 novel regions: chromosomes 2q21-q23 (P = .0033 for Caucasian subjects) and 8p23-p21 (P = .0011 for African American subjects). Three regions previously proposed as candidate regions for atopy, total IgE, or asthma also showed evidence for linkage to Der p-specific IgE responsiveness: 6p21 (P = .0064) and 13q32-q34 (P = 0.0064) in Caucasian subjects and 5q23-q33 (P = 0.0071) in African American subjects. CONCLUSIONS: No single locus generated overwhelming evidence for linkage in terms of established criteria and guidelines for a genome-wide screening, which supports previous assertions of a heterogeneous etiology for Der p-specific IgE responsiveness. Two novel regions, 2q21-q23 and 8p23-p21, that were identified in this study merit additional study.

Adult↗
PubMed1998

Evaluation of C-reactive protein, an inflammatory marker, and infectious serology as risk factors for coronary artery disease and myocardial infarction.

OBJECTIVES: We sought to test whether C-reactive protein (CRP) and seropositivity to any of three infectious agents are associated with angiographic coronary artery disease (CAD) and clinical myocardial infarction (MI). BACKGROUND: CRP, an inflammatory marker, is reported to predict risk of MI. The stimulus for CRP is unknown but might include infection. Chlamydia pneumoniae, cytomegalovirus and Helicobacter pylori have been linked to risk of MI or CAD. METHODS: Blood samples were collected from 363 patients undergoing coronary arteriography and tested for CRP and IgG titers to the infectious agents. RESULTS: CRP was higher in patients with CAD (1.32 mg/dl [SE 0.22, n = 80] vs. 0.58 mg/dl [SE 0.11 mg/dl, n = 109], p = 0.004) and in those with MI (2.05 mg/dl [SE 0.36, n = 47] vs. 0.54 mg/dl [SE 0.08, n = 133], p = 0.0002) than in respective control subjects. Seropositivity for each agent was present in a high proportion of patients with CAD (58% to 77%) or MI (54% to 75%) as well as in control subjects (no CAD: 46% to 74%; no MI: 50% to 77%). However, subjects seropositive to both C. pneumoniae and H. pylori had an increased prevalence of CAD (odds ratio [OR] 2.6, p = 0.02) and MI (OR 2.0, p = 0.15) and tended to have higher CRP levels (1.07 mg/dl [SE 0.16]) than those seronegative to both infectious agents (0.53 mg/dl [SE 0.10], p = 0.06). CONCLUSIONS: CRP is elevated in patients with CAD (more than twofold) and in those with MI (fourfold). Infectious serology is highly prevalent in both patients and control subjects. Seropositivity to both C. pneumoniae and H. pylori (but not one agent alone) may predict increased risk and may be associated with higher CRP levels. Infectious serology may be less predictive than previously suggested, but the cause of inflammation in CAD and MI deserves further study.

Adult↗
PubMed1998

Ketamine inhibits the proinflammatory cytokine-induced reduction of cardiac intracellular cAMP accumulation.

UNLABELLED: The proinflammatory cytokines, including tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma), are increased in heart failure and sepsis, clinical conditions for which the IV anesthetic ketamine is useful. The proinflammatory cytokines cause beta-adrenergic receptor (betaAR) hypofunction secondary to reduced function of the enzyme adenylylcyclase (AC). In this study, we evaluated the effect of ketamine alone, TNF-alpha and IFN-gamma, and ketamine plus TNF-alpha and IFN-gamma, on isoproterenol (ISO, a betaAR agonist) and forskolin (FSK, an activator of AC)-induced intracellular accumulation of cAMP. An in vitro culture of a rat heart cell line (H9c2) was labeled with [3H]adenine to produce [3H]ATP, and we measured the intracellular accumulation of [3H]cAMP after stimulation with ISO or FSK to convert the [3H]ATP to [3H]cAMP. Pretreatment with either cytokine alone did not significantly affect ISO or FSK-induced intracellular cAMP accumulation, whereas the combination of TNF-alpha and IFN-gamma caused a significant (P < 0.05 compared with untreated cells) reduction. Pretreatment with ketamine caused a significant (P < 0.05 compared with untreated cells) increase in ISO or FSK-induced cAMP accumulation. Pretreatment of the H9c2 cells with ketamine, plus the combination of TNF-alpha and IFN-gamma, inhibited the reduction of ISO or FSK-induced intracellular cAMP accumulation caused by the proinflammatory cytokines alone. These results demonstrate that the combination of the proinflammatory cytokines TNF-alpha and IFN-gamma reduce poststimulation (ISO or FSK) intracellular cAMP accumulation. This action of the proinflammatory cytokines is consistent with the observation of betaAR hyporesponsiveness to betaAR agonist therapy in sepsis and heart failure. Ketamine augments the poststimulation cAMP accumulation in H9c2 cells while inhibiting the cytokine-induced reduction of cAMP accumulation. This may partly explain the improvement in cardiac function after ketamine use in clinical conditions known to have increased systemic levels of proinflammatory cytokines, such as sepsis and heart failure. IMPLICATIONS: Tumor necrosis factor-alpha and interferon-gamma reduced poststimulation intracellular cAMP levels, whereas ketamine inhibits this action of the proinflammatory cytokines. Because cAMP is the second messenger for the beta-adrenergic receptor, this may be a mechanism for improved blood pressure and cardiac output in sepsis and heart failure after ketamine use.

Adrenergic beta-Agonists↗
PubMed1998

Kinetics and yield of singlet oxygen photosensitized by hypericin in organic and biological media.

The spectroscopy and photophysics of the photosensitizer hypericin when in homogeneous solutions and when bound to liposomes were studied. Hypericin was found to partition efficiently into DMPC liposomes, with a binding constant of 58 (mg lipid/mL)-1. In these liposomes the singlet oxygen production quantum yield was 0.43 +/- 0.09. To determine the deactivation constant of singlet oxygen in lipid bilayers for the first time, we calculated extrapolated values from its quenching by DMPC and lecithin in homogeneous solutions and obtained decay times of 36.4 and 12.2 microseconds, respectively. We also measured the quenching of singlet oxygen, sensitized by hypericin in DMPC liposomes, by NaN3, diphenyl isobenzofuran and H2O:D2O mixtures and explained the results on the basis of singlet oxygen diffusing rapidly out of the lipid bilayer into the aqueous medium. The observed temperature effect on the lifetime of singlet oxygen of about 50% over a 15 degrees C range in liposome suspension contrasts with a 3% change in a homogeneous solution in 1-nonanol and is explained by the temperature effect on the diffusion out of the liposome. A strong pH effect was observed, indicating that the deprotonated species formed above about pH 10 is a much weaker photosensitizer of singlet oxygen than the native, protonated species.

Anthracenes↗
PubMed1997

Why does thrombolysis fail? Breaking through the reperfusion ceiling.

With best current regimens, thrombolysis may initially fail in 15% to 40% of cases because of hemodynamic or mechanical factors, inadequate fibrinolysis, or failure to lyse platelet-rich thrombi. Pathophysiologic considerations and early experimental and clinical trials suggest that improved conjunctive antiplatelet therapy (as with glycoprotein IIb/IIIa inhibitors) and, possibly, more effective antithrombins (low molecular weight heparins, hirudin) may allow this thrombolysis "ceiling" to be broken and the goal achieved of reperfusion rates closer to those of primary angioplasty.

Angioplasty, Balloon, Coronary↗
PubMed1997

Modulation of alpha1B-adrenoceptor expression by agonist and protein kinase inhibitors.

The agonist-induced up-regulation of alpha1B-adrenoceptors in clone H99 of transfected Chinese hamster ovary cells that we reported previously (Zhu et al., 1996) was further investigated. Studies with a larger number of clones revealed that the up-regulation observed in H99 cells is atypical and that most other clones exhibit down-regulation under the same conditions. The role of protein kinases in the up-regulation of alpha1B-adrenoceptors in clone H99 was further investigated. Surprisingly, the protein kinase inhibitor staurosporine induced a similar up-regulation. Neither the selective protein kinase C inhibitor GF109203X nor the activator phorbol 12-myristate, 13-acetate altered receptor expression. The tyrosine kinase inhibitors genistein and its weaker analog daidzein did not induce up-regulation but blocked the up-regulation induced by epinephrine and by staurosporine. Up-regulation was blocked by the protein synthesis inhibitor cycloheximide. These studies suggest multiple mechanisms by which different protein kinases can modulate the expression of transfected alpha1B-adrenoceptors.

Adrenergic alpha-Agonists↗
PubMed1997

Changes in regional cerebral blood flow following light treatment for seasonal affective disorder: responders versus nonresponders.

BACKGROUND: Several brain imaging studies of antidepressant pharmacologic treatment utilizing single photon emission computed tomography (SPECT) have reported a normalization of deficits in cerebral blood flow (CBF) associated with recovery; other studies report no change, or a reduction in CBF following successful treatment. There have been no published SPECT studies of seasonal affective disorder (SAD) assessing response to light treatment in relation to changes in regional CBF (rCBF). In this study, we sought to test the hypothesis that increases in rCBF would be observed in SAD patients who responded to light treatment. METHODS: Ten depressed patients with SAD underwent functional brain imaging studies with 99mTc-hexamethylpropyleneamine oxime SPECT before and after light treatment. RESULTS: Relative increases in rCBF were observed in all brain regions compared to cerebellum in treatment responders, whereas nonresponders showed no change or decreases in rCBF relative to cerebellum. Significant differences in mean percentage change in rCBF between responders (n = 5) and nonresponders (n = 5) were detected in frontal and cingulate cortex, and thalamus. CONCLUSIONS: These findings provide preliminary support for the hypothesis that an increase in rCBF is associated with recovery from depression in SAD.

Adult↗
PubMed1997

A mutation in the methylenetetrahydrofolate reductase gene is not associated with increased risk for coronary artery disease or myocardial infarction.

OBJECTIVES: We sought to determine whether the C677T transition in the methylenetetrahydrofolate reductase (MTHFR) gene is associated with increased risk for coronary artery disease (CAD) or myocardial infarction (MI). BACKGROUND: Elevated plasma homocysteine has been identified as a risk factor for coronary atherosclerosis. Homocysteinemia may result from deficient MTHFR activity. A thermolabile form of MTHFR, associated with a C677T genetic transition, shows reduced activity and may be a risk factor for CAD. METHODS: Blood was withdrawn from patients undergoing coronary angiography, and DNA was extracted by a phenol-chloroform method. Genotyping was done by polymerase chain reaction (PCR) amplification of a 198-base pair segment of the MTHFR gene that brackets nucleotide 677. The amplicon was digested with the HinfI restriction enzyme. Products were visualized after electrophoresis in 1.5% agarose with ethidium bromide. RESULTS: Among 200 patients with a diagnosis of MI, the polymorphic allelic frequency was 33.3%, compared with 32.1% among 554 control subjects (p = 0.68); homozygosity was present in 11.5% of patients and 10.6% of control subjects (p = 0.74, odds ratio [OR] 1.09, 95% confidence interval [CI] 0.63 to 1.82). Among 510 patients with severe CAD (>60% stenosis), allelic frequency was 32.0%, compared with 34.8% for 168 subjects without CAD (<10% stenosis, p = 0.33); 11.2% of patients with CAD compared with 13.1% of control subjects were homozygous (p = 0.50, OR 0.83, 95% CI 0.5 to 1.40). CONCLUSIONS: Patients with angiographic evidence of CAD or clinical MI do not show an increased frequency of the C677T transition in the MTHFR gene. Our findings do not support this polymorphism as a risk factor for CAD or MI in a predominantly white, well nourished population of unrestricted age.

Adult↗
PubMed1997

Impact of the Food and Drug Administration approval of flecainide and encainide on coronary artery disease mortality: putting "Deadly Medicine" to the test.

In his book Deadly Medicine and on television, Thomas Moore impugns the process of antiarrhythmic drug approval in the 1980s, alleging that the new generation of drugs had flooded the marketplace and had caused deaths in numbers comparable to lives lost during war. To assess these important public health allegations, we evaluated annual coronary artery disease death rates in relation to antiarrhythmic drug sales (2 independent marketing surveys). Predicted mortality rates were modeled using linear regression analysis for 1982 through 1991. Deviations from predicted linearity were sought in relation to rising and falling class IC and overall class I antiarrhythmic drug use. Flecainide came to market in 1986 and encainide in 1987. Combined class IC sales peaked in 1987 and 1988 (maximum market penetration, 20%, first quarter 1989). Results of the Cardiac Arrhythmia Suppression Trial (CAST) were disclosed in April 1989. Overall annual class I antiarrhythmic prescription sales actually fell slightly (-3% to -4%/yr) in the 2 years before CAST and then more abruptly (- 12%) in the year after CAST (1990). Sales of class IC drugs fell dramatically after CAST (by 75%). Coronary death rates (age adjusted) fell in a linear fashion during the decade of 1982 through 1991. No deviation from predicted rates was observed during the introduction, rise, and fall in class IC (and other class I) sales: rates were 126/100,000 in 1985 (before flecainide), 114 and 110 in 1987 and 1988 (maximum sales), and 103 in 1990 (after CAST). Deviations in death rates in the postulated range of 6,000 to 25,000 per year were shown to be excluded easily by the 95% confidence intervals about the predicted rates. Entry of new antiarrhythmic drugs in the 1980s did not lead to overall market expansion and had no adverse impact on coronary artery disease death rates, which fell progressively. Thus, the allegations in Deadly Medicine could not be confirmed.

Anti-Arrhythmia Agents↗
PubMed1997

A comparison of the accuracy and reproducibility of digital three-dimensional coronary artery reconstructions using edge detection or videodensitometry.

Global quantitative three-dimensional measurements of coronary arteries may be helpful in determining the functional significance of various forms of coronary pathology. A computerized system has been developed that is capable of performing 3-D reconstruction of digitized images obtained from multiple coronary angiographic views using either automated edge detection (AED) or videodensitometric (VD) techniques. To compare the accuracy and reproducibility of measurements obtained from this system using either technique, stationary and moving coronary aluminum 3-D phantoms, each with 13 branches (diameter 0.58-6.35 mm, length 21.5-64.5 mm), were imaged and reconstructed 10 separate times each. Individual branch lengths and diameters were calculated and compared to each other and to known values. Diameter measurements were compared using either AED or VD. Intraclass correlation coefficients between observed values (ICC) for vessel length were r = 0.89 for the stationary and r = 0.97 for the moving phantom. ICCs for vessel diameter were r = 0.93 (AED) and r = 0.95 (VD) for the stationary and r = 0.98 (AED) and r = 0.97 (VD) for the moving phantom. Mean differences (+/-SD) between true and observed values [MDTO(+/-SD)] for vessel length were -1.0 +/- 3.9 mm for the stationary and -3.5 +/- 3.2 mm for the moving phantom. MDTO(+/-SD) for vessel diameter were -0.10 +/- 0.52 mm (AED) and +0.03 +/- 0.30 mm (VD) for the stationary and -0.21 +/- 0. 44 mm (AED) and -0.12 +/- 0.33 (VD) for the moving phantom. We conclude that the quantitative accuracy and reproducibility of measurements obtained by computerized 3-D reconstruction of coronary model phantoms is of high enough quality to warrant further clinical evaluation. VD appears to be more accurate than AED for measuring vessel diameter.

Aluminum↗
PubMed1997

Predictive value for future arrhythmic events of fractal dimension, a measure of time clustering of ventricular premature complexes, after myocardial infarction. CAST Investigators. Cardia Arrhythmia Suppression Trial.

OBJECTIVES: Our objective was to test fractal dimension (D), a measure of clustering of ventricular premature complexes (VPCs), on entry Holter recording as a predictor of future arrhythmic death and other-cause mortality in postinfarction patients in the Cardiac Arrhythmic Suppression Trial (CAST). BACKGROUND: Nonlinear dynamic methods of signal processing are being applied in medicine to provide new insights into apparently "chaotic" biologic events, including cardiac arrhythmias. One such application is the derivation of a fractal D to describe the clustering of VPCs in time. METHODS: Baseline Holter recordings were analyzed in blinded manner for 484 patients: 237 died or had a resuscitated cardiac arrest during follow-up, and 247 matched patients had no events. Fractal D, measured in four ways, was assessed as a predictor using Cox regression. RESULTS: One measure of D (high resolution D) was a significant univariate (relative hazard ratio 0.79 per SD change, p = 0.011) and multivariate (hazard ratio 0.75, p = 0.046) predictor of arrhythmic death but not other death (univariate p = 0.95, relative hazard 0.95, p = 0.66). Fractal D was greater (VPCs less clustered) in those patients free of arrhythmic events. On subgroup analysis, the predictive value of D resided in the randomized patient group (i.e., those who showed VPC suppression during initial antiarrhythmic drug titration and were randomized to blinded therapy with active drug or placebo) (multivariate hazard ratio 0.57, p = 0.001). CONCLUSIONS: A high resolution fractal D was predictive of arrhythmic (but not nonarrhythmic) death in a large postinfarction cohort. Further study of this new signal processing approach to ambulatory electrocardiographic recording will be of interest.

Aged↗
PubMed1997

"Rescue" utilization of abciximab for the dissolution of coronary thrombus developing as a complication of coronary angioplasty.

OBJECTIVES: This study sought to test the effect on thrombus score of the "rescue" utilization of the glycoprotein IIb/IIIa antagonist abciximab given to patients in whom intracoronary thrombus has developed as a complication after percutaneous transluminal coronary angioplasty (PTCA) and to determine its clinical utility. BACKGROUND: Abciximab is effective in the prevention of acute ischemic complications when given prophylactically to patients during high risk PTCA. However, its ability to therapeutically dissolve newly formed intracoronary thrombus occurring as a complication after PTCA is not known. METHODS: We performed an observational study in 29 consecutive patients who received abciximab (0.25 mg/kg body weight intravenous bolus, followed by a 12-h infusion at 10 microg/min) after attempted PTCA caused either the new development or further progression of thrombus. Angiograms were analyzed to determine thrombus score and Thrombolysis in Myocardial Infarction (TIMI) flow grade before and after abciximab. Procedural and clinical success and long-term outcome were also determined. RESULTS: Thrombus score decreased from 3.0 +/- 0.9 (mean +/- SD) to 0.86 +/- 0.92 (p < 0.001), and TIMI flow grade increased from 2.5 +/- 0.7 to 2.9 +/- 0.3 (p = 0.008). No instances of distal embolization or no-reflow were noted. The procedural success (< or = 50% residual stenosis) rate was 97%. The clinical success (procedural success with no in-hospital myocardial infarction, bypass surgery or death) rate was 93%. CONCLUSIONS: Dissolution of thrombus and restoration of TIMI grade 3 flow were readily achieved after administration of abciximab when delivered in a "rescue" manner after the development of thrombosis after PTCA. This novel use of abciximab will need to be validated in randomized trials.

Abciximab↗
PubMed1997

A mutation in the hamster alpha1B-adrenergic receptor that differentiates two steps in the pathway of receptor internalization.

An NP(X)nY motif is highly conserved among G protein-coupled receptors and is similar to an NPXY motif involved in receptor-mediated endocytosis for several non-G protein-coupled receptors. We investigated the role of this motif in alpha1B-adrenergic receptor function and regulation. Y348A alpha1B-adrenergic receptors in which this sequence was mutated from NPIIY to NPIIA were prepared by site-directed mutagenesis and transfected into Chinese hamster ovary cells. Binding of the antagonist prazosin to Y348A receptors was similar to that of wild-type receptors, but affinity of the Y348A receptors for the agonist epinephrine was increased by approximately 10-fold. Despite this increase in agonist binding affinity, the Y348A mutation completely uncoupled the receptors from stimulation of phosphoinositide hydrolysis and mobilization of intracellular Ca2+. Exposure of cells expressing Y348A receptors to the agonist epinephrine resulted in receptor "sequestration," defined as a loss of cell surface receptors accessible to radioligand in binding assays with intact cells on ice, similar to that for the wild-type receptor. In contrast, Y348A receptors did not undergo "endocytosis" into the light vesicle fraction in sucrose density gradient centrifugation assays, as did the wild-type receptor. These results (i) indicate an important role for Tyr348 in coupling the alpha1B-adrenergic receptor to G protein and subsequent effector activation, (ii) provide further evidence that alpha1B-adrenergic receptor internalization can be separated into a sequestration step and an endocytosis step, (iii) indicate that effector activation and second messenger formation are not required for the sequestration of these receptors but may be involved in endocytosis, and (iv) provide a useful new tool for further investigation of the nature of the subcellular compartments and the molecular modifications involved in the multiple steps involved in internalization of G protein-coupled receptors.

Animals↗
PubMed1997

Light reduction and the electroretinogram of preterm infants.

AIMS: To examine the effects of light on retinal development and function in preterm infants as measured by the electroretinogram (ERG). Secondary outcomes included visual acuity testing, the incidence of retinopathy of prematurity, and general wellbeing, reflected in feeding tolerance, rate of weight gain, and length of hospital stay. METHODS: Eligibility criteria for enrollment were birthweight < or = 1250 g and gestational age < or = 31 weeks. Sixty one infants were randomly allocated by 6 hours after birth to a control or treatment group which wore 97% light filtering goggles for a minimum of four weeks or until the infant reached 31 weeks postmenstrual age. RESULTS: There were no significant differences between the two groups in the numbers of electroretinograms performed at 36 weeks of postmenstrual age. Although the sample size was not large enough to exclude clinically important differences in secondary outcomes, no significant differences were observed between the groups in visual acuity testing at 4-6 months corrected age, incidence of retinopathy of prematurity, weight gain, or length of stay. CONCLUSION: These data support the safety and feasibility of this intervention. A much larger study will be needed to determine whether light reduction to the eyes of very low birthweight infants will reduce the incidence of retinopathy of prematurity or enhance general well-being.

Electroretinography↗