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Purpose: MANTIS is a Monte Carlo code developed for the detailed simulation of columnar CsI scintillator screens in x-ray imaging systems. Validation of this code is needed to provide a reliable and valuable tool for system optimization and accurate reconstructions for a variety of x-ray applications. Whereas previous validation efforts have focused on matching of summary statistics, in this work the authors examine the complete point response function (PRF) of the detector system in addition to relative light output values., Methods: Relative light output values and high-resolution PRFs have been experimentally measured with a custom setup. A corresponding set of simulated light output values and PRFs have also been produced, where detailed knowledge of the experimental setup and CsI:Tl screen structures are accounted for in the simulations. Four different screens were investigated with different thicknesses, column tilt angles, and substrate types. A quantitative comparison between the experimental and simulated PRFs was performed for four different incidence angles (0 degrees, 15 degrees, 30 degrees, and 45 degrees) and two different x-ray spectra (40 and 70 kVp). The figure of merit (FOM) used measures the normalized differences between the simulated and experimental data averaged over a region of interest., Results: Experimental relative light output values ranged from 1.456 to 1.650 and were in approximate agreement for aluminum substrates, but poor agreement for graphite substrates. The FOMs for all screen types, incidence angles, and energies ranged from 0.1929 to 0.4775. To put these FOMs in context, the same FOM was computed for 2D symmetric Gaussians fit to the same experimental data. These FOMs ranged from 0.2068 to 0.8029. Our analysis demonstrates that MANTIS reproduces experimental PRFs with higher accuracy than a symmetric 2D Gaussian fit to the experimental data in the majority of cases. Examination of the spatial distribution of differences between the PRFs shows that the main reason for errors between MANTIS and the experimental data is that MANTIS-generated PRFs are sharper than the experimental PRFs., Conclusions: The experimental validation of MANTIS performed in this study demonstrates that MANTIS is able to reliably predict experimental PRFs, especially for thinner screens, and can reproduce the highly asymmetric shape seen in the experimental data. As a result, optimizations and reconstructions carried out using MANTIS should yield results indicative of actual detector performance. Better characterization of screen properties is necessary to reconcile the simulated light output values with experimental data.

In this paper, we consider a prototype of an adaptive SPECT system, and we use simulation to objectively assess the system's performance with respect to a conventional, non-adaptive SPECT system. Objective performance assessment is investigated for a clinically relevant task: the detection of tumor necrosis at a known location and in a random lumpy background. The iterative maximum-likelihood expectation-maximization (MLEM) algorithm is used to perform image reconstruction. We carried out human observer studies on the reconstructed images and compared the probability of correct detection when the data are generated with the adaptive system as opposed to the non-adaptive system. Task performance is also assessed by using a channelized Hotelling observer, and the area under the receiver operating characteristic curve is the figure of merit for the detection task. Our results show a large performance improvement of adaptive systems versus non-adaptive systems and motivate further research in adaptive medical imaging.

The authors have designed and constructed a small-animal adaptive SPECT imaging system as a prototype for quantifying the potential benefit of adaptive SPECT imaging over the traditional fixed geometry approach. The optical design of the system is based on filling the detector with the region of interest for each viewing angle, maximizing the sensitivity, and optimizing the resolution in the projection images. Additional feedback rules for determining the optimal geometry of the system can be easily added to the existing control software. Preliminary data have been taken of a phantom with a small, hot, offset lesion in a flat background in both adaptive and fixed geometry modes. Comparison of the predicted system behavior with the actual system behavior is presented, along with recommendations for system improvements.

We are exploring the concept of adaptive multimodality imaging, a form of non-linear optimization where the imaging configuration is automatically adjusted in response to the object. Preliminary studies suggest that substantial improvement in objective, task-based measures of image quality can result. We describe here our work to add motorized adjustment capabilities and a matching CT to our existing FastSPECT II system to form an adaptive small-animal SPECT/CT.

Design in engineering begins with the problem of robustness-by what factor should intrinsic capacity exceed normal demand? Here we consider robustness for a neural circuit that crosses the retina from cones to ganglion cells. The circuit's task is to represent the visual scene at many successive stages, each time by modulating a stream of stochastic events: photoisomerizations, then transmitter quanta, then spikes. At early stages, the event rates are high to achieve some critical signal-to-noise ratio and temporal bandwidth, which together set the information rate. Then neural circuits concentrate the information and repackage it, so that nearly the same total information can be represented by modulating far lower event rates. This is important for spiking because of its high metabolic cost. Considering various measurements at the outer and inner retina, we conclude that the "safety factors" are about 2-10, similar to other tissues.

We have designed and constructed a small-animal adaptive SPECT imaging system as a prototype for quantifying the potential benefit of adaptive SPECT imaging over the traditional fixed geometry approach. The optical design of the system is based on filling the detector with the object for each viewing angle, maximizing the sensitivity, and optimizing the resolution in the projection images. Additional feedback rules for determining the optimal geometry of the system can be easily added to the existing control software. Preliminary data have been taken of a phantom with a small, hot, offset lesion in a flat background in both adaptive and fixed geometry modes. Comparison of the predicted system behavior with the actual system behavior is presented along with recommendations for system improvements.

Objectives: The purpose of the study was to examine long-term outcome after traditional surgical treatment of corrected transposition of the great arteries to provide a basis for comparison with new procedures, such as the double-switch or Senning-Rastelli procedures., Methods: Patient- and procedure-related variables in 123 patients with corrected transposition and 2 functional ventricles operated on between 1963 and 1996 were analyzed. Patients with intracardiac procedures underwent either a traditional 2-ventricle repair or a Fontan procedure., Results: The 1-, 5-, 10-, and 15-year survivals after the operation were 84%, 75%, 68%, and 61%, respectively. Patients requiring tricuspid valve replacement (27 patients) at any time during follow-up had a significantly worse outcome ( P < .001; hazard ratio, 4.4), whereas the best outcome was seen in patients undergoing the Fontan procedure (17 patients, 0 deaths). Right ventricular end-diastolic pressure of greater than 17 mm Hg before the operation ( P < .0001), complete heart block after the operation ( P = .001), subvalvular pulmonary stenosis ( P = .013), Ebstein malformation of the tricuspid valve ( P = .025), and preoperative systemic (right) ventricular dysfunction ( P = .041) were identified as risk factors for death at any time by means of univariate analysis. Ebstein malformation of the tricuspid valve ( P = .036; hazard ratio, 1.5) was identified as a risk factor for death by multivariate analysis., Conclusions: The long-term outcome of patients with corrected transposition after a classic surgical approach is unsatisfactory. The poorest outcome was seen in patients who required tricuspid valve replacement either at their initial operation or later during follow-up. Alternative surgical approaches, such as the double-switch, Senning-Rastelli, or Fontan procedures, are likely to have better long-term results, especially in the highest risk groups.

Objective: This open-label, active-controlled study investigated the cardiac safety and antihyperglycemic effect of rosiglitazone (RSG) in patients with type 2 diabetes., Research Design and Methods: Of the 203 patients randomly assigned to RSG (4 mg b.i.d.) or glyburide (GLB) (titrated to achieve optimal glycemic control for the first 8 weeks only to limit the risk of hypoglycemia; mean 10.5 mg/day), 118 had an echocardiogram performed at week 52. Left ventricular (LV) mass index, ejection fraction, and left ventricular end-diastolic volume were assessed by M-mode echocardiography at baseline and weeks 12, 28, and 52; 24-h ambulatory blood pressure was assessed at baseline and at weeks 28 and 52. Glycemic control was assessed by measuring fasting plasma glucose (FPG) and HbA(1c)., Results: Neither treatment produced an increase in LV mass index that exceeded 1 SD. Ejection fraction did not change in either group. Both groups had clinically insignificant increases in LV end-diastolic volume. RSG, but not GLB, caused a statistically significant reduction in ambulatory diastolic blood pressure. Both treatments reduced HbA(1c) and FPG., Conclusions: A total of 52 weeks of therapy with RSG (4 mg b.i.d.) did not adversely affect cardiac structure or function in patients with type 2 diabetes and produced significant and sustained reductions in hyperglycemia. Decreases in ambulatory diastolic blood pressure with RSG were superior to those with GLB.

The effect of rosiglitazone (Avandia [BRL 49653C]) on the pharmacokinetics of ethinylestradiol and norethindrone was evaluated after repeat dosing of rosiglitazone with an oral contraceptive (OC; Ortho-Novum 1/35 containing norethindrone 1 mg and ethinylestradiol 0.035 mg) in a randomized, double-blind, placebo-controlled crossover study. Thirty-four healthy female volunteers received oral rosiglitazone (RSG) 8 mg + OC or matched placebo (P) + OC daily on days 1 to 14 of a 28-day OC dosing cycle; the alternate regimen was administered during a second cycle. Ethinylestradiol and norethindrone pharmacokinetics were determined from plasma concentrations on day 14. Lack of pharmacokinetic effect was prospectively defined as 90% CI for the point estimate (PE) of the ratio (RSG + OC):(P + OC) contained within a 20% equivalence range for both ethinylestradiol and norethindrone (analyzed by ANOVA). For RSG + OC and P + OC, respectively, mean ethinylestradiol AUC(0-24) was 1126 and 1208 pg.h/mL (PE: 0.92; 90% CI: 0.88-0.97), and mean norethindrone AUC(0-24) was 178 and 171 ng.h/mL (PE: 1.04; 90% CI: 1.00-1.07). Thus, rosiglitazone had no significant effects on the pharmacokinetics of ethinylestradiol or norethindrone. Coadministration of rosiglitazone with OCs does not induce metabolism of these synthetic sex steroids and is not expected to impair the efficacy of OCs or hormone replacement therapy.

Objectives: To investigate whether treatment with acarbose alters the pharmacokinetics (PK) of coadministered rosiglitazone., Methods: Sixteen healthy volunteers (24-59-years old) received a single 8-mg dose of rosiglitazone on day 1, followed by 7 days of repeat dosing with acarbose [100 mg three times daily (t.i.d.) with meals]. On the last day of acarbose t.i.d. dosing (day 8), a single dose of rosiglitazone was given with the morning dose of acarbose. PK profiles following rosiglitazone dosing on days 1 and 8 were compared, and point estimates (PE) and associated 95% confidence intervals (CI) were calculated., Results: Rosiglitazone absorption [as measured with peak plasma concentration (Cmax) and time to peak concentration (Tmax)] was unaffected by acarbose. The area under the concentration-time curve from time zero to infinity [AUC(0-infinity)] was on average 12% lower (95% CI-21%, -2%) during rosiglitazone + acarbose coadministration and was accompanied by an approximate 1-h (23%) reduction in terminal elimination half-life t1/2 (4.9 h versus 3.8 h). This small decrease in AUC(0-infinity) appears to be due to an alteration in systemic clearance of rosiglitazone and not changes in absorption. These observed changes in AUC(0-infinity) and t1/2 are not likely to be clinically relevant. Coadministration of rosiglitazone and acarbose was well tolerated., Conclusion: Acarbose administered at therapeutic doses has a small, but clinically insignificant, effect on rosiglitazone pharmacokinetics.

Background: An estimated 15 million adults in the United States are affected by dysphagia (difficulty swallowing). Severe dysphagia predisposes to medical complications such as aspiration pneumonia, bronchospasm, dehydration, malnutrition, and asphyxia. These can cause death or increased health care costs from increased severity of illness and prolonged length of stay. Existing modalities for treating dysphagia are generally ineffective, and at best it may take weeks to months to show improvement. One common conventional therapy, application of cold stimulus to the base of the anterior faucial arch, has been reported to be somewhat effective. We describe an alternative treatment consisting of transcutaneous electrical stimulation (ES) applied through electrodes placed on the neck., Objective: Compare the effectiveness of ES treatment to thermal-tactile stimulation (TS) treatment in patients with dysphagia caused by stroke and assess the safety of the technique., Methods: In this controlled study, stroke patients with swallowing disorder were alternately assigned to one of the two treatment groups (TS or ES). Entry criteria included a primary diagnosis of stroke and confirmation of swallowing disorder by modified barium swallow (MBS). TS consisted of touching the base of the anterior faucial arch with a metal probe chilled by immersion in ice. ES was administered with a modified hand-held battery-powered electrical stimulator connected to a pair of electrodes positioned on the neck. Daily treatments of TS or ES lasted 1 hour. Swallow function before and after the treatment regimen was scored from 0 (aspirates own saliva) to 6 (normal swallow) based on substances the patients could swallow during a modified barium swallow. Demographic data were compared with the test and Fisher exact test. Swallow scores were compared with the Mann-Whitney U test and Wilcoxon signed-rank test., Results: The treatment groups were of similar age and gender (p > 0.27), co-morbid conditions (p = 0.0044), and initial swallow score (p = 0.74). Both treatment groups showed improvement in swallow score, but the final swallow scores were higher in the ES group (p > 0.0001). In addition, 98% of ES patients showed some improvement, whereas 27% of TS patients remained at initial swallow score and 11% got worse. These results are based on similar numbers of treatments (average of 5.5 for ES and 6.0 for TS, p = 0.36)., Conclusions: ES appears to be a safe and effective treatment for dysphagia due to stroke and results in better swallow function than conventional TS treatment.

Wegener's Granulomatosis is an autoimmune disease characterized by a rare form of systemic vasculitis which can result in damage to vital organs of the body by restricting blood flow to those organs. It affects various systems of the body including the central nervous system and cranial nerves. To our knowledge, there are no previous described cases of oropharyngeal dysphagia in these patients. This paper describes and discusses a case of oropharyngeal dysphagia in a patient with Wegener's Granulomatosis.

This study evaluated the efficacy and safety of rosiglitazone monotherapy in patients with type 2 diabetes. After a 4-week placebo run-in period, 493 patients with type 2 diabetes were randomized to receive rosiglitazone [2 or 4 mg twice daily (bd)] or placebo for 26 weeks. The primary end point was change in hemoglobin A(1c); other variables assessed included fasting plasma glucose, fructosamine, endogenous insulin secretion, urinary albumin excretion, serum lipids, and adverse events. Rosiglitazone (2 and 4 mg bd) decreased mean hemoglobin A(1c) relative to placebo by 1.2 and 1.5 percentage points, respectively, and reduced fasting plasma glucose concentrations relative to placebo by 3.22 and 4.22 mmol/L, respectively. Fasting plasma insulin and insulin precursor molecules decreased significantly. Homeostasis model assessment estimates indicate that rosiglitazone (2 and 4 mg bd) reduced insulin resistance by 16.0% and 24.6%, respectively, and improved ss-cell function over baseline by 49.5% and 60.0%, respectively. Urinary albumin excretion decreased significantly in the rosiglitazone (4 mg bd) group. There was no increase in adverse events with rosiglitazone. In the short-term, rosiglitazone is an insulin sensitizer that is effective and safe as monotherapy in patients with type 2 diabetes who are inadequately controlled by lifestyle interventions.

Rosiglitazone is a potent insulin-sensitizing oral hypoglycemic agent of the thiazolidinedione class that works through activation of the peroxisome proliferator-activated receptor-gamma (PPAR-gamma) nuclear receptor and improves glycemic control in patients with non-insulin-dependent diabetes mellitus. The potential for a drug-drug interaction with oral digoxin was investigated. Subjects received both of the study regimens in a random sequence: digoxin 0.375 mg plus matching placebo for rosiglitazone orally each morning for 14 days or digoxin 0.375 mg plus 8 mg rosiglitazone orally each morning for 14 days. There was a 14-day washout period between sessions. Blood and urine were collected over 24 hours beginning on the morning of day 14 for measurement of digoxin concentrations. An equivalence statistical approach was used, with rosiglitazone considered to have no effect on the pharmacokinetics of digoxin if the 90% confidence interval (CI) for the ratio of digoxin plus rosiglitazone relative to digoxin plus placebo was completely contained within the range (0.80, 1.25) for the primary end points, AUC(0-24), and C24. Digoxin AUC(0-24) and C24 values were similar for digoxin 0.375 mg plus matching placebo (18.5 ng.h/mL and 0.579 ng/mL, respectively) and digoxin 0.375 mg plus rosiglitazone (19.1 ng.h/mL and 0.594 ng/mL, respectively). Point estimates were 1.05 (90% CI: 1.01, 1.10) for AUC(0-24) and 1.04 (90% CI: 0.98, 1.11) for C24. Oral and renal clearance were also similar between regimens. Digoxin alone or in combination with rosiglitazone was safe and well tolerated. The most common adverse experience was headache. Coadministration of digoxin with rosiglitazone had no significant effect on the safety or steady-state pharmacokinetics of digoxin.

Rosiglitazone is a potent oral antidiabetic agent of the thiazolidinedione class that works through activation of the peroxisome proliferator-activated nuclear receptor. It improves insulin sensitivity in peripheral tissues and effectively lowers blood glucose in patients with type 2 diabetes. Metformin is a dimethyl-biguanide, also used in type 2 diabetes, that lowers fasting blood glucose primarily by decreasing hepatic glucose output. Rosiglitazone and metformin reduce plasma glucose concentrations via different mechanisms and thus could potentially be used in combination to optimize glycemic control. This study evaluated the effects of the coadministration of these two agents on the pharmacokinetics of both rosiglitazone and metformin. Sixteen male volunteers (22-55 years old) received oral metformin (500 mg every 12 hours), rosiglitazone (2 mg every 12 hours), or the combination each for 4 days. Plasma collected on day 4 of each regimen was assayed for rosiglitazone and metformin concentrations. Oral doses of rosiglitazone and metformin were safe and well tolerated when administered alone or in combination. There were no clinically significant episodes of hypoglycemia or increased blood lactic acid levels following treatment with any regimen. Coadministration of rosiglitazone and metformin had no significant effects on the steady-state pharmacokinetics (AUC(0-12 h), Cmax, tmax, or t1/2) of either drug. The authors conclude that rosiglitazone can be safely administered with metformin and, due to the different mechanisms of action of these agents, may offer a therapeutic advantage in patients with type 2 diabetes mellitus.

Objective: Our purpose was to describe the outcome of the Rastelli repair in D -transposition of the great arteries and to determine the risk factors associated with unfavorable events., Methods: From March 1973 to April 1998, 101 patients with D -transposition of the great arteries and ventricular septal defect underwent a Rastelli type of repair. Median age and weight were 3.1 years (10th to 90th percentiles 0.3-9.9 years) and 12.8 kg (5.9-28.2). Pulmonary stenosis was present in 73 patients and pulmonary atresia in 18; 10 patients had no left ventricular outflow tract obstruction., Results: There were 7 early deaths (7%) and no operative deaths in the last 7 years of the study. Risk factors for early death, by univariable analysis, included straddling tricuspid valve (P =.04) and longer aortic crossclamping times (P =.04). At a median follow-up of 8.5 years, there were 17 late deaths and 1 patient had undergone heart transplantation. Forty-four patients had reoperations for conduit stenosis, 11 for left ventricular outflow tract obstruction, and 28 had interventional catheterization to relieve conduit stenosis. Nine patients had late arrhythmias, and there were 5 sudden deaths. Overall freedom from death or transplantation (Kaplan-Meier) was 82%, 80%, 68%, and 52% at 5, 10, 15, and 20 years, respectively. Freedom from death or reintervention (catheterization or surgical treatment) was 53%, 24%, and 21% at 5, 10, and 15 years of follow-up, respectively., Conclusions: The Rastelli repair can be performed with low early mortality. However, substantial late morbidity and mortality are associated with conduit obstruction, left ventricular outflow tract obstruction, and arrhythmia.

The cone signal reaches the cat's On-beta (X) ganglion cell via several parallel circuits (bipolar cell types b1, b2, and b3). These circuits might convey different regions of the cone's temporal bandwidth. To test this, I presented a step of light that elicited a transient depolarization followed by a sustained depolarization. The contribution of bipolar cells to these response components was isolated by blocking action potentials with tetrodotoxin and by blocking inhibitory synaptic potentials with bicuculline and strychnine. Stationary fluctuation analysis of the sustained depolarization gave the rate of quantal bombardment: approximately 5100 quanta sec(-1) for small central cells and approximately 45,000 quanta sec(-1) for large peripheral cells. Normalizing these rates for the vastly different numbers of bipolar synapses (150-370 per small cell vs 2000 per large cell), quantal rate was constant across the retina, approximately 22 quanta synapse(-1) sec(-1). Nonstationary fluctuation analysis gave the mean quantal EPSP amplitude: approximately 240 microV for the transient depolarization and 30 microV for the sustained depolarization. The b1 bipolar cell is known from noise analysis of the On-alpha ganglion cell to have a near-maximal sustained release of only approximately two quanta synapse(-1) sec(-1). This implies that the other bipolar types (b2 and b3) contribute many more quanta to the sustained depolarization (>/=46 synapse(-1) sec(-1)). Type b1 probably contributes large quanta to the transient depolarization. Thus, bipolar cell types b1 and b2/b3 apparently constitute parallel circuits that convey, respectively, high and low frequencies.

To determine the rate and statistics of light-evoked transmitter release from bipolar synapses, intracellular recordings were made from ON-alpha ganglion cells in the periphery of the intact, superfused, cat retina. Sodium channels were blocked with tetrodotoxin to prevent action potentials. A light bar covering the receptive field center excited the bipolar cells that contact the alpha cell and evoked a transient then a sustained depolarization. The sustained depolarization was quantified as change in mean voltage (Deltav), and the increase in voltage noise that accompanied it was quantified as change in voltage variance (Deltasigma(2)). As light intensity increased, Deltav and Deltasigma(2) both increased, but their ratio held constant. This behavior is consistent with Poisson arrival of transmitter quanta at the ganglion cell. The response component attributable to glutamate quanta from bipolar synapses was isolated by application of 6-cyano-7-nitroquinoxaline (CNQX). As CNQX concentration increased, the signal/noise ratio of this response component (Deltav(CNQX)/Deltasigma(CNQX)) held constant. This is also consistent with Poisson arrival and justified the application of fluctuation analysis. Two different methods of fluctuation analysis applied to Deltav(CNQX) and Deltasigma(CNQX) produced similar results, leading to an estimate that a just-maximal sustained response was caused by approximately 3,700 quanta s(-1). The transient response was caused by a rate that was no more than 10-fold greater. Because the ON-alpha cell at this retinal locus has approximately 2,200 bipolar synapses, one synapse released approximately 1.7 quanta s(-1) for the sustained response and no more than 17 quanta s(-1) for the transient. Consequently, within the ganglion cell's integration interval, here calculated to be approximately 16 ms, a bipolar synapse rarely releases more than one quantum. Thus for just-maximal sustained and transient depolarizations, the conductance modulated by a single bipolar cell synapse is limited to the quantal conductance ( approximately 100 pS at its peak). This helps preserve linear summation of quanta. The Deltav/Deltasigma(2) ratio remained constant even as the ganglion cell's response saturated, which suggested that even at the peak of sensory input, summation remains linear, and that saturation occurs before the bipolar synapse.

A retinal ganglion cell commonly expresses two spatially overlapping receptive field mechanisms. One is the familiar "center/surround," which sums excitation and inhibition across a region somewhat broader than the ganglion cell's dendritic field. This mechanism responds to a drifting grating by modulating firing at the drift frequency (linear response). Less familiar is the "nonlinear" mechanism, which sums the rectified output of many small subunits that extend for millimeters beyond the dendritic field. This mechanism responds to a contrast-reversing grating by modulating firing at twice the reversal frequency (nonlinear response). We investigated this nonlinear mechanism by presenting visual stimuli to the intact guinea pig retina in vitro while recording intracellularly from large brisk and sluggish ganglion cells. A contrast-reversing grating modulated the membrane potential (in addition to the firing rate) at twice the reversal frequency. This response was initially hyperpolarizing for some cells (either ON or OFF center) and initially depolarizing for others. Experiments in which responses to bars were summed in-phase or out-of-phase suggested that the single class of bipolar cells (either ON or OFF) that drives the center/surround response also drives the nonlinear response. Consistent with this, nonlinear responses persisted in OFF ganglion cells when ON bipolar cell responses were blocked by L-AP-4. Nonlinear responses evoked from millimeters beyond the ganglion cell were eliminated by tetrodotoxin. Thus, to relay the response from distant regions of the receptive field requires a spiking interneuron. Nonlinear responses from different regions of the receptive field added linearly.

To examine the effects of repeat oral dosing of rosiglitazone on the pharmacokinetics of nifedipine, a prototype CYP3A4 substrate, a randomized, open-label, crossover study was performed with two treatment phases separated by a washout period of at least 14 days. Twenty-eight healthy male volunteers received either a single 20 mg oral nifedipine dose or rosiglitazone 8 mg orally once daily for 14 days with a single 20 mg oral nifedipine dose administered on day 14. Plasma nifedipine concentrations were determined over the 24-hour period following administration of the nifedipine doses. Lack of effect was defined as the demonstration that the 90% CI was contained entirely within a symmetrical 30% range either side of unity on the loge-scale. Following rosiglitazone + nifedipine administration, the area under the nifedipine concentration-time curve from time zero to infinity (AUC(0-infinity)) was 13% lower than that after administration of nifedipine alone. This difference in nifedipine AUC(0-infinity) was not deemed to be clinically significant since the 90% CI was contained within the protocol-defined 30% range (point estimate for ratio of geometric means 0.87; 90% CI: 0.79, 0.96). Rosiglitazone had no marked effect on nifedipine peak plasma concentration (point estimate: 0.99; 90% CI: 0.73, 1.34) or time to peak concentration compared with nifedipine alone. Rosiglitazone coadministration produced a small decrease in the mean nifedipine half-life (point estimate: -0.77; 90% CI: mean difference -1.29 h, -0.25 h). Both treatment regimens were well tolerated and associated with a favorable safety profile. Rosiglitazone, at the highest dose used in clinical studies, produced a small, clinically insignificant decrease in nifedipine exposure. The very small effect on nifedipine pharmacokinetics suggests that rosiglitazone is an extremely weak inducer of CYP3A4, a characteristic that distinguishes rosiglitazone from troglitazone.

Study Design: The effects of orally administered eprosartan on changes induced by angiotensin II in blood pressure, renal hemodynamics, and aldosterone secretion were evaluated in healthy men in this double-blind, randomized, single-dose, placebo-controlled crossover study, which was conducted in three parts. Part 1 (n = 12) assessed the onset and duration of the effect of eprosartan 350 mg or placebo; part 2 (n = 14) assessed the dose-response profile of placebo or 10, 30, 50, 70, 100 or 200 mg eprosartan; and part 3 (n = 5) assessed the duration of the effect of 50, 100, or 350 mg eprosartan., Results: In part 1 of the study; 350 mg eprosartan caused complete inhibition of angiotensin II-induced pressor and renal blood flow hemodynamic effects (effects on effective renal plasma flow [ERPF]) and inhibited angiotensin II-induced stimulation of aldosterone secretion from 1 to 3 hours after administration. Eprosartan, 350 mg, inhibited the effects of exogenous angiotensin II by approximately 50% to 70% from 12 to 15 hours after dosing. Eprosartan had no angiotensin II agonistic activity and produced an increase in ERPF starting at 1 to 4 hours after dosing. In study part 2, at 3 hours after single doses of 10, 30, 50, 70, 100, and 200 mg, eprosartan inhibited angiotensin 11-induced decreases in ERPF by 39.1%, 49.9%, 33.0%, 56.0%, 71.0%, and 85.7%, respectively, compared with placebo. In study part 3, 50, 100, and 350 mg eprosartan produced measurable Inhibition of angiotensin II-induced decreases in ERPF from 12 to 15 hours after administration. In parts 2 and 3, the eprosartan angiotensin II antagonism on blood pressure response and aldosterone secretion mirrored the angiotensin II antagonism on ERPF.

Unlabelled: This review provides information on health and biological effects of low-dose radiation to help institutional review boards and investigators make educated assessments of the risks of low-level radiation exposure involved in research, particularly in children., Methods: Studies of low-level radiation exposure with large sample sizes and long follow-up were reviewed. To help interpret the studies, we clarified the measures and measurement strategies of radiation exposure and of health risks. The few large studies of risks of low-level radiation in children have failed to detect an increased incidence of cancer. Most studies of low-level radiation involve adults., Results: The risk of increased rates of cancer after low-level radiation exposure is not supported by population studies of health hazards from exposure to background radiation, radon in homes, radiation in the workplace or radiotherapy. Compared to the frequency of daily spontaneous genetic mutations, the biological effect of low-level radiation at the cellular level seems extremely low. Furthermore, the potentiation of cellular repair mechanisms by low-level radiation may result in a protective effect from subsequent high-level radiation. Studies approved by institutional review boards in the U.S. that involve the exposure of healthy normal children to ionizing radiation were reviewed., Conclusion: Health risks from low-level radiation could not be detected above the "noise" of adverse events of everyday life. In addition, no data were found that demonstrated higher risks with younger age at low-level radiation exposure.

SK&F107647 is a synthetic hematoregulatory peptide (HP) increases both the number and function of progenitor cells, enabling improved survival after lethal myelosuppression, lethal fungal infection, and lethal herpes simplex virus infection in murine models. This Phase I single-blind placebo-controlled dose-rising crossover trial examined the efficacy of SK&F107647 in patients who had incurable solid tumor malignancies. Sixteen patients were treated. Six adverse events in 3 patients were considered to be possibly related to SK& F107647; all were mild to moderate in nature (mild nervousness and agitation at 0.01 ng/kg, moderate fever and mild nausea at 0.1 ng/kg, elevated hepatic enzymes at 0.1 ng/kg, and mild vomiting at 1.0 ng/kg). Plasma half-life was 2.44 hours (+/-1.07 standard deviation). The observed area volume of distribution was 16.7 L (+/-7.7 standard deviation) and clearance was 5.04 L/hour (+/-1.83 standard deviation). When administered as a single 2-hour intravenous infusion at doses ranging from 0.01 to 100 ng/kg, SK&F107647 is safe and well tolerated.

The potential for eprosartan, a nonbiphenyl tetrazole angiotensin II receptor antagonist, to affect the 24-hour plasma glucose profiles in type II diabetic patients treated with glyburide was investigated in this randomized, placebo-controlled, double-blind (eprosartan-placebo phase only), two-period, period-balanced, crossover study. All patients received a stable oral dose (3.75-10 mg/day) of glyburide for at least 30 days before the first dose of double-blind study medication was administered. Patients were randomized to receive either 200-mg oral doses of eprosartan twice daily or matching oral placebo doses concomitantly with glyburide for 7 days during each treatment period. After a minimum washout period of 14 days, patients were crossed over to the alternate treatment. Serial samples to measure glucose concentrations in plasma were collected over a 24-hour period on the day before administration of eprosartan or placebo and again on day 7. Mean glucose concentrations were comparable between treatment groups before administration of eprosartan or placebo. The point estimate (90% confidence interval) for the ratio of the average mean 24-hour plasma glucose concentrations of eprosartan + glyburide to placebo + glyburide after 7 days of administration was 0.96 (0.90, 1.01). Eprosartan did not significantly alter the 24-hour plasma glucose profile in patients with type II diabetes mellitus who were previously stabilized on glyburide.

Purpose: To study the pharmacokinetics of SK&F 107647, a novel hematoregulatory agent, in rats, dogs, and patients with non-lymphoid solid tumor malignancy., Methods: Sprague Dawley rats and beagle dogs (n = 6 each; 3 M, 3 F) were given 25 mg/kg of SK&F 107467 as an iv bolus injection, and patients (n = 6; 4 M, 2 F) received 100 mg/kg as a 2 hour iv infusion. Plasma samples were assayed for drug using either HPLC (rat and dog) or RIA (human)., Results: In each species the plasma clearance (CL) of SK&F 107647 was low in relation to hepatic blood flow, and the volume of distribution (Vd ss) was reflective of distribution to extracellular body water. The plasma CL in humans was near that of average glomerular filtration rate. Using allometric equations for interspecies scaling (Y = a.W(b)), body-weight normalized human pharmacokinetic data were reasonably predicted using either the body weight normalized rat or the dog data. The allometric exponents (b) for CL, Vd(ss), and T(1/2) of SK&F 107647 were 0.63, 0.94, and 0.29, respectively., Conclusions: Use of a limited pool of available animal data allowed for reasonable predictions of human pharmacokinetics of SK&F 107647.

Early tracheal extubation in the operating room after atrial septal defect (ASD) surgery was recommended as part of a clinical practice guideline (CPG) established in the Cardiovascular Program at the Children's Hospital, Boston, MA. This retrospective review was undertaken to determine whether this practice was efficient without compromising patient care. The charts and hospital charges for 102 patients undergoing secundum ASD or sinus venosus defect surgery between March 1992 and July 1994 were reviewed; 36 patients (Group I) had surgery prior to introduction of the CPG, and 66 patients were managed according to the CPG. Of the latter, 25 patients (Group II) were tracheally extubated in the operating room (OR) and 41 patients (Group III) were extubated in the cardiac intensive care unit (CICU). Patients in all three groups were similar with respect to height, weight, and surgical conditions including cardiopulmonary bypass time, lowest esophageal temperature, hematocrit, total OR time, and the time from completion of bypass to leaving the OR. Patients in Group II received significantly less fentanyl during anesthesia, were more likely to have a respiratory acidosis on admission to the CICU, and had an increased frequency of vomiting in the CICU. There was no difference in duration of CICU stay among groups. The length of hospital stay was reduced in Groups II and III after introduction of the CPGs, but was not influenced by tracheal extubation in the OR. There was no difference among groups in the hospital charges for OR, anesthesia and CICU time. However, when the combined hospital charges for services provided both in the OR and CICU were included, patients in Group II were charged significantly less, and this primarily reflects the absence of postoperative mechanical ventilation charges. Tracheal extubation in the OR after ASD surgery in children can result in lower patient charges without significantly compromising patient care.

Objectives: This study sought to determine whether adjunctive balloon angioplasty after rotational atherectomy and excimer laser angioplasty provides better lumen enlargement ("facilitated angioplasty") than angioplasty alone., Background: Adjunctive angioplasty is often used immediately after atherectomy and laser angioplasty to further enlarge lumen dimensions, but it is not known whether this practice is superior to angioplasty alone., Methods: Balloon angioplasty was performed in 1,266 native coronary lesions alone (n = 541) or after extraction atherectomy (n = 277), rotational atherectomy (Rotablator) (n = 211) or excimer laser angioplasty (n = 237). Quantitative angiographic analysis included final lumen diameter, final diameter stenosis and efficiency of balloon-mediated lumen enlargement., Results: Compared with angioplasty alone (33 +/- 12% [mean +/- SD]), final diameter stenosis was higher for adjunctive angioplasty after extraction atherectomy (37 +/- 16%, p < 0.001) and excimer laser angioplasty (37 +/- 16%, p < 0.001) and lower after rotational atherectomy (27 +/- 15%, p < 0.001). However, there was significant undersizing of balloons after all three devices. To correct for differences in balloon size, the efficiency index (final lumen diameter/balloon diameter ratio) was calculated and was higher for adjunctive angioplasty after the Rotablator (0.78 +/- 0.14, p < 0.001) than after angioplasty alone (0.69 +/- 0.12). The efficiency indexes suggested facilitated angioplasty after rotational atherectomy for ostial, eccentric, ulcerated and calcified lesions and lesions > 20 mm long. Facilitated angioplasty was also observed after extraction atherectomy and excimer laser angioplasty for ostial lesions, but not for any other lesion subsets., Conclusions: Rotational atherectomy, extraction atherectomy and excimer laser angioplasty can facilitate the results of balloon angioplasty. However, the extent of facilitated angioplasty is dependent on the device and baseline lesion morphology, consistent with the need for lesion-specific coronary intervention.

We studied the morphology, photic responses, and synaptic connections of ON-OFF amacrine cells in the cat retina by penetrating them with intracellular electrodes, staining them with horseradish peroxidase, and examining them with the electron microscope. In a sample of seven cells, we found two different morphological types: the A19, which ramifies narrowly in stratum 2 (sublamina a) of the inner plexiform layer, and the A22, which ramifies mostly in stratum 4 (sublamina b) but extends some dendrites to sublamina a. Both of these cell types have axon-like processes that extend > 800 microns from the conventional dendritic arbor. ON-OFF amacrine cells in our sample had receptive fields (1.7 +/- 0.3 mm diameter) that were broader than their dendritic arbors (425 +/- 35 microns diameter) and that extended over the region of axon-like processes. In addition, we found many features in common with ON-OFF amacrine cells in poikilotherm vertebrates: a broad receptive field without surround antagonism, two sizes of spike-like events, narrow dynamic range (1 log unit intensity), and excitatory postsynaptic potentials at light on and light off. Two A19 amacrine cells were examined in the electron microscope: most synaptic inputs (93 and 76%, respectively) to either cell were from amacrine cells, with minor inputs from cone bipolar cells. Synaptic outputs were to bipolar, amacrine, and ganglion cells, including the OFF-alpha cell.

Plasma very-low density lipoprotein (VLDL) and vitellogenin (VTG) from mature female Japanese quail (Coturnix coturnix japonica) and chickens (Gallus domesticus) were isolated and digested in vitro with cathepsin D (EC3.4.23.5). The incubation mixtures were then reduced and subjected to gradient (4.5-18%) SDS-polyacrylamide gel electrophoresis. Protein fragments were stained with either Coomassie Brilliant Blue R-250 (VLDL digests) or Coomassie Brilliant Blue R-250 containing 20 mM AlCl3 (VTG digests). Fragments resulting from the in vitro enzymatic digestion of quail and chicken plasma VLDL-apolipoprotein B (apo B) and VTG closely resembled those produced in vivo and isolated from egg yolks of each respective species. Phosvitin, a proteolytically derived fragment of VTG, primarily existed as a single band (M(r) approximately 42 kDa) in Japanese quail yolk granules. In contrast, chicken phosvitin mainly consisted of a cluster of phosphoproteins ranging in size from approximately 37 to 45 kDa. In addition to reporting a novel species difference in phosvitin moieties, the present study is the first to examine the role of cathepsin D in the generation of egg yolk proteins from plasma precursors in Japanese quail. Confirmatory evidence also was provided concerning the important role of this aspartic endopeptidase in the proteolytic cleavage of plasma VLDL-apo B and VTG in the chicken.

In response to environmental changes brought about by the debate over health-care reform, hospitals are seeking means to decrease costs while improving quality. By examining the process of health-care delivery, problems in the system can be highlighted for further investigation. Development of clinical practice guidelines by an interdisciplinary team can be an effective approach to decrease undesirable practice variation, standardize appropriate resource use, and measure the effectiveness of care through defined expected-patient outcomes. By ensuring the appropriate, efficient, and effective delivery of health care, savings in cost can be realized by the elimination of duplication, rework, and waste.

The pharmacokinetic profile of penciclovir was determined after a single 500-mg dose of its oral precursor, famciclovir, in 9 healthy volunteers and in 14 patients with chronic hepatic disease. Plasma and urine samples were analyzed for concentrations of penciclovir and 6-deoxy-penciclovir using a reverse-phase high-performance liquid chromatography (HPLC) method. Famciclovir was not quantifiable in patients with hepatic disease, and 6-deoxy-penciclovir was quantifiable in only a limited number of specimens. The extent of systemic availability of penciclovir, as measured by AUC0-infinity, was similar in patients with hepatic disease and in healthy subjects. In contrast, Cmax was significantly lower (average decrease of 43%) in subjects with hepatic disease relative to healthy normal subjects. Median Tmax for subjects with hepatic disease was significantly increased (by 0.75 hours) compared with subjects with normal liver function. These data suggest a decrease in the rate, but not the extent, of systemic availability of penciclovir in patients with hepatic disease. It should be unnecessary to modify the dose of famciclovir for subjects with compensated hepatic disease and normal renal function.

Nonsteroidal antiinflammatory drugs differ with respect to their effects on prostaglandin metabolism in various tissues, a property that may be partly responsible for some of the differences in the pharmacologic activities and side-effect profiles that are associated with their use. The effects of nabumetone on urinary prostaglandin excretion have not been reported. Fourteen healthy females, age 21-43 years, were treated with nabumetone (NAB) 1000 mg daily, sulindac (SUL) 200 mg every 12 hours, and indomethacin (IND) 50 mg every 12 hours for 7 days in a randomized period-balanced crossover study. The effects of drug treatment on urinary prostaglandin excretion (PGE2, 6-keto-PGF1 alpha, PGF2 alpha, thromboxane [TX] B2) and platelet function (collagen-induced whole blood platelet aggregation [CIPA] and template bleeding time) were determined on day 1 and day 7. For each treatment regimen, mean baseline urinary PG excretion values were comparable for each prostanoid, but the pattern of excretion differed in response to each drug. Treatment with NAB significantly increased the urinary excretion rates of PGE2 and PGF2 alpha, but 6-keto-PGF1 alpha and TXB2 excretion were unchanged. IND treatment did not result in a significant change in PGE2 excretion but did significantly reduce urinary 6-keto-PGF1 alpha and TXB2 excretion rates. Reduced excretion of PGF2 alpha was observed on both study days during treatment with IND and SUL. SUL treatment also resulted in increased urinary PGE2 excretion while significantly reducing 6-keto-PGF1 alpha excretion on day 7. Significant differences were observed between the NAB and SUL regimens with respect to PGF2 alpha excretion and between the NAB and SUL regimens for PGE2, PGF2 alpha, 6-keto-PGF alpha 1 (on day 1 only) and TXB2 (on day 1 only). Neither NAB nor SUL caused inhibition of CIPA or bleeding time although platelet aggregation was inhibited during IND treatment. That NAB treatment was neither associated with alterations in platelet function nor decreases in the urinary excretion of the vasodilatory prostaglandins, PGE2 and 6-keto-PGF1 alpha, suggests that NAB possesses renal sparing properties.

SKF 107260 is a potent pentapeptide antagonist of the platelet membrane glycoprotein receptor GP IIb/IIIa. The in vitro platelet inhibitory effects of SKF 107260, acetylsalicylic acid (ASA), and their combination, on collagen-induced platelet aggregation and secretion (ATP release) were assessed in human whole blood. Additionally, the concentration-response relationships for these inhibitors were compared for males and females in order to explore gender differences in platelet responsiveness. SKF 107260 caused a concentration-dependent inhibition of platelet aggregation which was significant at concentrations > or = 30 nM. ASA also caused a concentration-dependent inhibition of platelet aggregation which was significant at concentrations > or = 1 mg/dl. The addition of ASA 1 mg/dl to increasing concentrations of SKF 107260 resulted in a more pronounced inhibition of platelet aggregation than when either agent was used alone. These data suggest a pharmacologic interaction, especially at SKF 107260 concentrations < or = 30 nM. Since ATP release was significantly inhibited at concentrations > or = 1 nM, platelet secretion appears to be more sensitive than aggregation to inhibition by SKF 107260. These data suggest that platelet secretion in response to collagen is dependent on the aggregation response mediated by GP IIb/IIIa. In conclusion, SKF 107260 is a potent inhibitor of both whole blood platelet aggregation and secretion and these anti-aggregatory effects may be augmented by concomitant ASA administration.

The ACC has affirmed its commitment to universal access to health care. Underserved populations exist in urban and rural centers. Common to each is a paucity of personnel trained in cardiovascular care and a lack of access to preventive and highly technologic services. These factors contribute to a poor health outcome (75). Part of the rural problem can be corrected by the transfer of information to local providers by the use of new information systems. Included would be real-time electronic consultation, on-site subspecialty visits and the appropriate use of nonphysician providers (15). The urban problem requires changes in priorities and responsibilities of the academic health centers toward the communities they serve. Curricula changes of cardiovascular specialists, internists, generalists and nonphysician health care personnel must include diversity in training, physician training of ethnically matched providers in addition to technical excellence and research into methods of patient education and motivation for a healthier life-style (51). Reimbursement must appropriately reward those caring for underserved patients and those providing evaluation and management services (43,52).

Objective: To characterize the pharmacokinetics of a single 500 mg oral dose of famciclovir in subjects with varying degrees of renal impairment., Methods: Twenty-seven subjects were enrolled in an open-label parallel-group study. Eighteen patients had renal impairment (average age [ +/- SD], 49 +/- 12 years), and nine subjects were healthy volunteers (average age, 28 +/- 7 years). Patients with renal impairment were stratified into groups based on estimated creatinine clearance (CLCR): mild impairment (CLCR, 60 to 80 ml/min/1.73 m2), moderate impairment (CLCR, 30 to 59 ml/min/1.73 m2) and severe impairment (CLCR, 5 to 29 ml/min/1.73 m2). Plasma and urine specimens were analyzed for concentrations of penciclovir, the antivirally active metabolite of famciclovir, by reverse-phase HPLC. Plasma data were analyzed with use of model-independent methods., Results: In subjects with normal renal function (CLCR > 80), the mean maximum plasma concentrations of penciclovir was 2.83 micrograms/ml (range, 1.30 to 3.82 micrograms/ml) and the mean time to reach maximum concentration was 0.89 hours (range, 1/2 to 1 1/2 hours). The mean apparent terminal elimination half-life was 2.15 hours (range, 1.56 to 2.87 hours). A linear relationship was observed between the plasma elimination rate constant and CLCR and between renal clearance and CLCR. Mean area under the plasma concentration-time curve from zero to infinity was approximately tenfold higher and the plasma elimination rate constant was approximately fourfold lower in patients with severe renal impairment than in subjects with normal renal function., Conclusion: Consideration should be given to modification of the dosing schedule of famciclovir from the usual 8-hour interval to a 12-hour interval for patients with moderate renal impairment (CLCR 30 to 59 ml/min/1.73 m2) or a 24-hour interval for patients with severe renal impairment (CLCR < 30 ml/min/1.73 m2).

Our objectives were to determine procedural success, clinical complications, and follow-up restenosis rates after rotational burr and transluminal extraction atherectomy of coronary artery and saphenous vein graft ostial stenoses. Balloon angioplasty of ostial lesions has been associated with low rates of success and high rates of clinical complications and restenosis compared to nonostial lesions. Atherectomy, due to its ability to excise (extraction atherectomy) or pulverize (rotational atherectomy) atheroma and the internal elastic lamina, may result in improved procedural outcome. We retrospectively studied 101 patients with ostial stenoses treated by rotational burr and transluminal extraction atherectomy over a 3-yr period. Quantitative angiography and clinical follow-up were reviewed to determine success, complication, and restenosis rates. Rotational burr (n = 29) and transluminal extraction (n = 72) atherectomy were associated with high procedural success (93% and 90%, respectively) and a low incidence of complications (6.9% and 4.2%, respectively). Post-atherectomy angiographic success was low (52% and 69%, respectively) and required adjunctive balloon angioplasty in 85% of patients overall. This lower success rate likely reflects device undersizing as the overall post-atherectomy artery to device ratio was near unity (0.95). The rates of angiographic ostial restenosis remain high (39.1% and 65.9%, respectively, P < 0.05). The high rate of restenosis after transluminal extraction atherectomy was due to the higher rate of restenosis in saphenous vein grafts (80%) compared to TEC treated coronary arteries (59%). When only coronary artery lesions were compared, there was no significant difference between atherectomy device groups with respect to restenosis rates or late loss.(ABSTRACT TRUNCATED AT 250 WORDS)

When a bar of light (215 x 5000 microns) illuminates the receptive field of an ON-beta ganglion cell of cat retina, the cell depolarizes. Intracellular recording from the cat eyecup preparation shows that this depolarization is due to an increase in conductance (2.4 +/- 0.6 nS). Different phases of this depolarization have different reversal potentials, but all of these reversal potentials are more positive than the cell's resting potential in the dark. When the light is turned on, there is an initial transient depolarization; the reversal potential measured for this transient is positive (23 +/- 11 mV). As the light is left on, the cell partially repolarizes to a sustained depolarization; the reversal potential measured for this sustained depolarization is close to zero (-1 +/- 5 mV). When the light is turned off, the cell repolarizes further; the reversal potential measured for this repolarization is negative (-18 +/- 7 mV), but still above the resting potential in the dark (-50 mV). To explain this variety of reversal potentials, at least two different synaptic conductances are required: one to ions which have a positive reversal potential and another to ions which have a negative reversal potential. Comparing the responses to broad and narrow bars suggests that these two conductances are associated with the center and surround, respectively. Finally, since an ON-beta cell in the area centralis receives about 200 synapses, these results indicate that a single synapse produces an average conductance increase of about 15 pS during a near-maximal depolarization.

Objectives: The purpose of this study was to determine whether residual stenoses after excimer laser angioplasty and atherectomy were due to inefficient tissue ablation/removal or to undersized devices., Background: Significant residual stenoses are commonly observed after use of laser and atherectomy devices. It is not known whether these residual stenoses are due to inefficient or undersized devices., Methods: To determine the relative contribution of these factors, the minimal lumen diameter, percent diameter stenosis and normal reference diameter were measured immediately before and after coronary interventions in 696 lesions, including transluminal extraction atherectomy, high speed mechanical rotational atherectomy, excimer laser angioplasty and conventional balloon angioplasty. The ratio of the diameter of the device to the normal reference diameter (D/A, a measure of device sizing) and the ratio of the residual lumen diameter after use of the device to the device diameter (RLD/D, a measure of the efficiency of lumen enlargement) were calculated., Results: Baseline diameter stenoses were similar for all interventions. The percent diameter stenoses were greater immediately after extraction atherectomy (60 +/- 21%), rotational atherectomy (54 +/- 23%) and excimer laser angioplasty (61 +/- 18%) compared with balloon angioplasty (26 +/- 12%, p < 0.001). The D/A ratio was smaller after extraction atherectomy (0.63 +/- 0.14), rotational atherectomy (0.59 +/- 0.17) and excimer laser angioplasty (0.51 +/- 0.11) compared with balloon angioplasty (1.05 +/- 0.13, p < 0.001). The RLD/D ratio was similar after extraction atherectomy (0.73 +/- 0.24) and balloon angioplasty (0.71 +/- 0.11) but was greater after rotational atherectomy (0.92 +/- 0.16, p < 0.001) and excimer laser angioplasty (0.85 +/- 0.30, p < 0.01) compared with balloon angioplasty., Conclusions: Residual stenoses after extraction atherectomy, rotational atherectomy and excimer laser angioplasty were more severe than after balloon angioplasty but were due to undersized devices (low D/A ratio), not to inefficient devices (low RLD/D ratio). Rotational atherectomy and excimer laser angioplasty were more efficient (higher RLD/D) than balloon angioplasty, whereas extraction atherectomy and balloon angioplasty were similar.

Advances in the diagnosis and therapy of congenital heart disease in the past few decades have allowed the survival of young adults who are a fertile substrate for developing bacterial endocarditis. In addition to valvular involvement, young adults with congenital disease may develop infection on the ventricular septum, or in a vascular shunt, a patent ductus arteriosus, or coarctation of the aorta. The incidence of endocarditis in children and adults with congenital heart disease is higher than with rheumatic heart disease or mitral valve prolapse. Infecting organisms, diagnosis, and therapy are similar to acquired heart disease, but the physiologic variations and patient population often add a unique flavor to the management of this group.

Inability to cross the site of occlusion with a guidewire is the most common cause of failed angioplasty. The Glidewire, a kink-resistant, flexible wire with a hydrophilic coating, was applied to 71 (59 total, 12 subtotal) refractory occlusions, resulting in an overall angioplasty success rate of 45%. The Glidewire may improve the success rate for PTCA of total and subtotal occlusions that cannot be crossed with conventional guidewires.

Two challenge trials and one confirmation trial were conducted to evaluate the efficacy of spectinomycin in the treatment of 1-day-old ducklings infected with Escherichia coli. In the challenge trials, ducklings were injected in the right posterior thoracic air sac with 0.2 cm3 of broth containing 10(8) colony-forming units E. coli (strain O78, E38)/ml. Spectinomycin at dosage levels of 2.5 mg, 5.0 mg, and 10.0 mg of activity was injected subcutaneously 6 hours following infection. The confirmation trial was conducted to confirm the challenge trials; procedures were similar to those used in the challenge trials, except that only the 5.0 mg of activity dosage of spectinomycin was used. In both types of trials, spectinomycin-treated ducklings had significantly lower mortality and higher average weight gain, average daily gain, and feed consumption than infected unmedicated controls. These results indicate that spectinomycin is effective in treating ducks for experimentally induced colibacillosis caused by E. coli (strain O78, E38).

Because acetylsalicylic acid (ASA, aspirin) is a common antipyretic drug, there has been considerable research on the effects of ASA on mammalian embryonic development. However, very limited research has been conducted on the effects of ASA on avian development and hatchability. The present study investigated the effect of dietary ASA on fertility and hatchability and whether embryos of breeder hens fed ASA, as compared with embryos of hens fed a control diet, would survive elevated temperatures during incubation. White Leghorn layer breeders were fed 0, .025, .050, .100, .200, and .400% ASA for the first 13 mo of egg production. When averaged over 13 mo, hens fed .40% dietary ASA demonstrated a decline in fertility (P < .03), hatchability of fertile eggs (P < .04), and hatchability of eggs set (P < .02). Chicks from hens fed .10% ASA weighed more than chicks from hens receiving 0, .025, .20, or .40% ASA (P < .01). When embryos were incubated at elevated temperatures of 42.8 or 43.3 C for 5.5 to 12 h on Day 16 of incubation, hatchability declined. Also, ASA fed to layer breeders did not improve hatchability of embryos exposed to elevated incubation temperatures when compared with embryos exposed to a control incubation temperature (37.2 C). During Month 9 of production, chicks from hens fed .05 and .10% ASA and exposed to an elevated temperature of 42.8 C for 9 h on Day 16 of incubation weighed more than similarly heat-stressed chicks of hens fed 0, .20, or .40% ASA (temperature by diet interaction, P < .03).(ABSTRACT TRUNCATED AT 250 WORDS)

White Leghorn breeder hens were fed 0, .05, or .40% acetylsalicylic acid (ASA) for either 1 wk or 1 mo. Blood samples were collected 4 h postentrance of an egg into the uterus (baseline) and at oviposition of a hardshelled (HS) egg. Plasma samples were analyzed for prostaglandin (PG) F2 alpha by radioimmunoassay. Peripheral PGF2 alpha concentrations peaked upon oviposition of a HS egg in both ASA-fed hens as well as the controls (0% ASA). The levels of dietary ASA and the duration of time the ASA was administered did not affect baseline or peak PGF2 alpha concentrations. It was concluded that either the timing or route of administration of ASA resulted in the failure of ASA to effectively reduce peak peripheral PGF2 alpha concentrations.