Characteristics, management, and midterm outcome in infants with atrioventricular nodal reentry tachycardia

OBJECTIVE: To further validate an antibody-capture ELISA for measuring bovine coronavirus (BCV) exposure (antibody seroresponse) in cattle and to explain the apparent loss of sensitivity of a BCV antigen-capture ELISA when testing feces from adult versus neonatal cattle. ANIMALS: 98 adult cows from herds with and without winter dysentery; 10 gnotobiotic or colostrum-deprived calves. PROCEDURES: Results of an antibody-capture ELISA for BCV and a plaque reduction virus neutralization assay performed on paired serum samples from 24 cattle were compared with each other and with results of immunoelectron microscopy (IEM) of feces for BCV. For samples from 98 cattle, results of antibody-capture ELISA were compared with results of IEM. Calves were inoculated with feces ELISA-positive or IEM-positive for BCV and monitored for BCV infection. An ELISA was developed to detect BCV antigen-antibody complexes in feces and results were compared with results of an antigen-capture ELISA and IEM. RESULTS: Antibody-capture ELISA results correlated with neutralization assay results, but agreed more closely with results of IEM. Calves became infected with BCV following inoculation with either ELISA-positive or ELISA-negative but IEM-positive feces. Results of the antigen-antibody ELISA correlated with results of IEM and the antigen-capture ELISA. CLINICAL IMPLICATIONS: In adult cattle, testing of paired serum samples by use of an antibody-capture ELISA may be a better indicator of recent BCV exposure than results of virus neutralization tests. Antigen-antibody binding in feces may interfere with results of antigen-capture ELISA for BCV.     

Effects of local budesonide treatment on the cell-mediated immune response in acute and relapsing colitis in rats

Glucocorticosteroids (GCS) are effective in treatment of inflammatory bowel disease (IBD), but also have unwanted systemic side effects. Here, we describe the effects of budesonide and dexamethasone on acute experimental colitis and on T cells in thymus and spleen, as well as the effect of budesonide treatment on relapsing colitis. Acute colitis was induced by intracolonic administration of 2,4,6-trinitrobenzene sulfonic acid (TNBS) in ethanol, and a relapse was induced by an intraperitoneal booster of TNBS. GCS were administered intrarectally on days 1, 4, and 6 after induction of acute colitis or a relapse. Inflammatory cells in the colon were studied on day 7, and in acute colitis also on days 13 and 16. Budesonide treatment in acute and relapsing colitis resulted in reduction of macroscopic damage and decreased the numbers of macrophages and neutrophils in the colon. Dexamethasone was less effective. Dexamethasone, but not budesonide, reduced the number of T cells in the thymus. It is concluded that local budesonide is more effective in treatment of acute experimental colitis than dexamethasone and, in contrast to dexamethasone, did not cause a general suppression of T cells. Although budesonide was very effective in the treatment of relapsing colitis, this effect was not accomplished by affecting the number of T cells in the colon.     

Frequent progesterone receptor immunoreactivity in tuberous sclerosis-associated renal angiomyolipomas

Angiomyolipomas can occur sporadically or in association with tuberous sclerosis complex (TSC). TSC is an autosomal dominant disorder characterized by seizures, mental retardation, and benign tumors of the brain, heart, kidney, and skin. Angiomyolipomas are more common in women than in men, suggesting a possible hormonal influence on tumor growth. In this study, 35 angiomyolipomas from 23 patients were immunostained with antibodies to estrogen receptor (ER) and progesterone receptor (PR). Eleven angiomyolipomas (31%) contained clusters of PR-immunoreactive smooth muscle cells. None contained ER-immunoreactive cells. Of the 21 tumors from patients with TSC, 11 (48%) were PR immunoreactive. All of the PR-immunoreactive angiomyolipomas were from women younger than 50 years of age, and all except one of these women had TSC. This study suggests that hormonal factors play a role in the pathogenesis of TSC-associated angiomyolipomas.     

Leukocyte differentials predict short-term clinical outcome following antipsychotic treatment in schizophrenia

PURPOSE: The purpose of the test-retest phase of the Collaborative Longitudinal Evaluation of Keratoconus (CLEK) Study was to determine the repeatability of the various parts of the CLEK Study protocol. This paper presents the test-retest parameters of the refraction protocol. METHODS: We examined 138 CLEK Study-eligible patients on two occasions (median, 90 days; range, 22 to 268 days). All patients underwent subjective refraction on two occasions, and contact lens over-refractions were performed either over the patient's habitual rigid contact lenses or over a trial rigid contact lens equal in base curve to the steep keratometric reading in nonrigid contact lens wearers. RESULTS: Mean interoccasion differences +/- SD were -0.32 +/- 2.91 D and -0.17 +/- 1.39 D for subjective refraction sphere and cylinder power, respectively, and the mean absolute difference for subjective refraction cylinder axis was 18.1 +/- 20.2 degrees. The mean interoccasion difference +/- SD for high-contrast visual acuity with subjective refraction was 0.38 +/- 10.9 letters correct. Mean interoccasion differences +/- SD were -0.11 +/- 0.81 D and 0.02 +/- 0.67 D for contact lens over-refraction sphere and cylinder power, respectively, and the mean absolute difference for contact lens over-refraction cylinder axis was 11.6 +/- 9.9 degrees. The mean interoccasion difference +/- SD for visual acuity with contact lens over-refraction was 0.50 +/- 5.2 letters correct and 0.71 +/- 6.9 letters correct for high- and low-contrast visual acuity, respectively. CONCLUSIONS: The repeatability of subjective refraction in keratoconus patients is good but somewhat lower than that found in nondiseased eyes. Only 36% of our repeat measures of sphere power from subjective refraction fell within 0.50 D of each other, compared with more than 90% in studies of normal eyes.     

Usefulness of multiplane transesophageal echocardiography to improve the assessment of severity of mitral regurgitation

This study was designed to examine the accuracy of multiplane transesophageal echocardiography (TEE) color Doppler measurements in comparison to monoplane or biplane measurements in estimating the severity of mitral regurgitation (MR). Multiplane TEE potentially increases diagnostic accuracy of transesophageal examinations; it is unknown if multiplane is more accurate in assessing the severity of MR than monoplane or biplane TEE. Left ventricular cineangiograms of 91 patients with MR (40 no or mild, 30 moderate, and 21 severe) were compared with systolic pulmonary venous flow reversal and transesophageal color Doppler measurements: jet area and length in the transverse and longitudinal plane, maximal and average of those 2 planes (biplane), and maximal and average of 11 different planes (multiplane). Flow reversal (16 patients) identified severe MR with a specificity of 96% and a sensitivity of 62%; these were 96% and only 10% to 43%, respectively, for color Doppler measurements. In the absence of flow reversal, multiplane maximal jet area predicted severe MR with a sensitivity of 88% and a specificity of 75%, which were 85% and 76%, respectively, for no or mild MR; this did not differ significantly from results obtained by monoplane or biplane measurements. Color Doppler measurements of eccentric jets were not reliable for identification of severe MR. Systolic pulmonary venous flow reversal identifies 2 of 3 patients with severe MR with a high accuracy. In patients without flow reversal, multiplane color Doppler TEE is very capable of assessing MR severity, but biplane and monoplane TEE are equally accurate.     

The role of the amygdala and dorsal raphe nucleus in mediating the behavioral consequences of inescapable shock

It has been argued that exposure to inescapable shock produces later behavioral changes such as poor shuttle box escape learning because it leads to the conditioning of intense fear, which later transfers to the shuttle box test situation and interferes with escape. Both fear, as assessed by freezing, and escape were measured in Sprague-Dawley rats 24 hr after exposure to inescapable shock. Lesions of the basolateral region and central nucleus of the amygdala eliminated the fear that transfers to the shuttle box after inescapable shock, as well as the fear conditioned in the shuttle box by the shuttle box shocks. However, the amygdala lesions did not reduce the escape learning deficit produced by inescapable shock. In contrast, dorsal raphe nucleus lesions did not reduce the fear that transfers to the shuttle box after inescapable shock, but eliminated the enhanced fear conditioning in the shuttle box as well as the escape deficit. The implications of these results for the role of fear and anxiety in mediating inescapable shock effects are discussed.     

Restenosis rates in diabetic patients: a comparison of coronary stenting and balloon angioplasty in native coronary vessels

BACKGROUND: Diabetes is a major risk factor for restenosis after coronary balloon angioplasty. Recent studies have shown that coronary stenting significantly reduces restenosis compared with balloon angioplasty alone. However, limited information is available on the effect of coronary stenting in diabetic patients. METHODS AND RESULTS: We designed this study to analyze the effect of diabetes on restenosis in patients treated with either balloon angioplasty or coronary stenting who were enrolled in a 6-month angiographic follow-up program. Three hundred consecutive patients, 19% of whom were diabetics, who underwent coronary stent implantation during a single-vessel procedure on native coronary vessels and who had 6-month angiographic follow-up constituted the study group (stent group). Three hundred consecutive patients who underwent 6-month angiographic follow-up after single-vessel conventional balloon angioplasty served as control patients (balloon group). Preprocedural, postprocedural, and follow-up angiograms were analyzed with quantitative angiography. In the balloon group, the restenosis rate was almost twofold higher in diabetic than in nondiabetic patients (63% versus 36%; P=.0002) owing to both a greater late loss (0.79+/-0.70 versus 0.41+/-0.61 mm, respectively; P<.0001) and a higher rate of late vessel occlusion (14% versus 3%, respectively; P<.001). In the stent group, restenosis rates were similar in diabetics and nondiabetics (25% versus 27%, respectively). Furthermore, in the stent group, late loss (0.77+/-0.65 versus 0.79+/-0.57 mm, respectively) and the rate of late vessel occlusion (2% versus 1%, respectively) did not differ significantly between diabetic and nondiabetic patients. CONCLUSIONS: Although diabetics have increased rates of restenosis and late vessel occlusion after simple balloon angioplasty, they have the same improved outcome with coronary stenting that has been documented in nondiabetic patients.     

Discovery of a novel, selective, and orally bioavailable class of thrombin inhibitors incorporating aminopyridyl moieties at the P1 position

A novel class of thrombin inhibitors incorporating aminopyridyl moieties at the P1 position has been discovered. Four of these thrombin inhibitors (13b,c,e and 14d) showed nanomolar potency (Ki 0.8-12 nM), 300-1500-fold selectivity for thrombin compared with trypsin, and good oral bioavailability (F = 40-76%) in rats or dogs. The neutral P1 was expected to increase metabolic stability and oral absorption. Identification of this novel aminopyridyl group at P1 was a key step in our search for a clinical candidate.     

Efficacy of radiofrequency ablation for control of intraatrial reentrant tachycardia in patients with congenital heart disease

BACKGROUND: Intraatrial reentrant tachycardia (IART) is a common problem in patients with congenital heart disease (CHD). The progression of clinical symptoms of IART and their response to radiofrequency (RF) ablation are not yet well described. OBJECTIVES: The objective of the study was to determine the early and midterm success rates of RF ablation in effecting a reduction of clinical arrhythmic events in patients with IART and CHD. METHODS: Clinical records of patients undergoing early, successful RF ablation were analyzed retrospectively to document the occurrence and frequency of documented IART, cardioversion and arrhythmia-related hospital visits before and after ablation. RESULTS: Fifty-five catheterizations for intended RF ablation of IART were performed in 45 patients (mean [+/-SD] age 24.5 +/- 10.5 years, 40 after surgical palliation of CHD). Early success was achieved for one or more IART circuits in 33 patients (73%). Mean clinical follow-up of those patients with successful ablation is 17.4 +/- 11.3 months (total 574 patient-months). Documented IART recurrence was noted after 21 (53%) of 40 early, successful catheterizations in 17 (52%) of 33 patients, with a mean time to recurrence of 4.1 months, often with electrocardiographically novel configurations. A more prolonged and frequent history of IART was a univariate risk factor for recurrence. Seven patients underwent repeat RF ablations, and eight patients were restarted on antiarrhythmic medications after ablation. Two patients who had severe ventricular dysfunction before RF ablation died 1.5 and 11 months after RF ablation without known arrhythmia recurrence. Clinical events related to IART increased steadily in frequency for 24 months before RF ablation. Radiofrequency ablation resulted in a reduction of event frequency to levels significantly lower than those in the 12-month period before RF ablation and not significantly different from those levels observed at baseline 3 to 4 years before RF ablation. CONCLUSIONS: In patients with successful RF ablation, the frequency of subsequent events was reduced compared with the 2 preceding years. However, recurrence of IART in patients who showed clinical improvement was frequent, and often revealed the presence of new IART configurations.