Adjunctive therapy with oxcarbazepine in children with partial seizures. The Oxcarbazepine Pediatric Study Group.

OBJECTIVE: To evaluate the safety and efficacy of oxcarbazepine (OXC) as adjunctive therapy in children with inadequately controlled partial seizures on one or two concomitant antiepileptic drugs (AEDs). BACKGROUND: OXC has shown antiepileptic activity in several comparative monotherapy trials in newly diagnosed patients with epilepsy, and in a placebo-controlled monotherapy trial in hospitalized patients evaluated for epilepsy surgery. DESIGN: A total of 267 patients were evaluated in a multicenter, randomized, placebo-controlled trial consisting of three phases: 1) a 56-day baseline phase (patients maintained on their current AEDs); 2) a 112-day double-blind treatment phase (patients received either OXC 30-46 mg/kg/day orally or placebo); and 3) an open-label extension phase. Data are reported only from the double-blind treatment phase; the open-label extension phase is ongoing. METHODS: Children (3 to 17 years old) with inadequately controlled partial seizures (simple, complex, and partial seizures evolving to secondarily generalized seizures) were enrolled. RESULTS: Patients treated with OXC experienced a significantly greater median percent reduction from baseline in partial seizure frequency than patients treated with placebo (p = 0.0001; 35% versus 9%, respectively). Forty-one percent of patients treated with OXC experienced a > or =50% reduction from baseline in partial seizure frequency per 28 days compared with 22% of patients treated with placebo (p = 0.0005). Ninety-one percent of the group treated with OXC and 82% of the group treated with placebo reported > or =1 adverse event; vomiting, somnolence, dizziness, and nausea occurred more frequently (twofold or greater) in the group treated with OXC. CONCLUSION: OXC adjunctive therapy administered in a dose range of 6 to 51 mg/kg/day (median 31.4 mg/kg/day) is safe, effective, and well tolerated in children with partial seizures.

Regulation of disease susceptibility: decreased prevalence of IgE-mediated allergic disease in patients with multiple sclerosis.

The development of restricted cytokine profiles by subsets of CD4+ T cells is a pivotal point in the regulation of immune responses. T cells producing Th1 cytokines (IL-2 and interferon-gamma) induce cell-mediated immunity, whereas T cells producing Th2 cytokines (IL-4, IL-5, and IL-10) play a prominent role in the induction of humoral immunity. We examined a group of patients with multiple sclerosis, a disease caused by excess production of Th1 cytokines in myelin-reactive T cells, and control patients with noninflammatory neuroconvulsive disorders, for the presence of allergic disease, which is caused by excess production of Th2 cytokines in allergen-specific T cells. The patients with multiple sclerosis had significantly fewer allergic symptoms, a lower number of positive allergen-specific IgE test results, and lower composite allergy indexes than control subjects. These results demonstrate that the prevalence of IgE-mediated allergic disease is decreased in a group of patients with multiple sclerosis and support the hypothesis that genetic factors that promote susceptibility to Th1-mediated inflammatory disease in human beings protect against the development of Th2-mediated disease.

Sudden development of intraoperative left ventricular outflow obstruction: differential and mechanism. An intraoperative two-dimensional echocardiographic study.

Systolic anterior motion (SAM) of the mitral valve, once considered to be pathognomonic of hypertrophic cardiomyopathy, has been reported in the absence of asymmetric septal hypertrophy. Of the 1,000 open heart operations performed with intraoperative two-dimensional epicardial echocardiography monitoring, four patients developed intraoperative dynamic left ventricular outflow obstruction associated with systolic anterior motion of the mitral valve that was not present preoperatively: three cases of mitral valve annuloplasty with Carpentier ring insertion and one of coronary artery bypass grafting. Though no patient had asymmetric septal hypertrophy or echocardiographic evidence of outflow obstruction by either preoperative cardiac catheterization or echocardiography, intraoperative two-dimensional epicardial echocardiography revealed SAM, and hyperdynamic left ventricles with three of these patients having documented left ventricular outflow tract gradients causing hemodynamic compromise. (Case 4 was hemodynamically stable following mitral valve repair, but had SAM and significant residual mitral regurgitation [MR] requiring reinstitution of cardiopulmonary bypass and re-repair). Measurement of mitral annular dimension demonstrated a normal decrease in size from diastole to systole in control operative subjects but not in the patients who developed outflow obstruction. The pathophysiology, treatment, and role of intraoperative echocardiography of dynamic left ventricular outflow tract obstruction are discussed.

Intraoperative evaluation of valvular regurgitation: comparison of echocardiographic techniques.

Intraoperative echocardiography provides information on cardiac structure and function that is unobtainable from routine monitoring modalities. Intraoperative imaging can be performed from the epicardial and/or transesophageal approach, and with the addition of contrast and/or color flow Doppler mapping, blood flow characteristics within the cardiac chambers can be visualized. The relative severity of regurgitation can be assessed before and after valvular surgery, and before the patient leaves the operating room, thereby facilitating successful valve repair or replacement. Surgeon preference, equipment availability, and valvular pathology will determine which technique will be utilized.

Comparison of phenotyping and genotyping of lymphoid neoplasms.

Comparison of phenotyping (PT) and genotyping (GT) of lymphoid neoplasms was performed on 51 specimens including lymph nodes, bone marrows, and body fluids. PT was performed with a flow cytometer using a large monoclonal antibody panel. GT included the testing for gene rearrangements of heavy chain, kappa and lambda light chains, and T-cell receptor beta-chain genes with DNA probes. The results obtained from these two techniques were generally compatible in terms of clonality and cell lineage. Only one case of B-cell lymphoma was not diagnosed by PT but showed gene rearrangement. For T-cell lymphoma, GT offers a more definitive diagnosis than does PT. Biclonality was demonstrated in one case of hairy cell leukemia by GT only. The rearranged band also offers a definitive clonal identification based on electrophoretic mobility. GT can detect a monoclonal population as small as 5% and can be performed on old or fresh specimens. PT requires 20% abnormal cells and a fresh specimen. It is concluded that GT is superior to PT for lymphoid tumor diagnosis, but it should be reserved as a supplementary test at this stage because of its technical complexity.

The necessity for tricuspid valve repair can be determined intraoperatively by two-dimensional echocardiography.

Residual significant tricuspid regurgitation after mitral valve operations may significantly increase postoperative morbidity and mortality. However, routine techniques to detect tricuspid regurgitation preoperatively and intraoperatively are inaccurate. Two-dimensional echocardiography was performed intraoperatively to assess its ability to evaluate and quantify the severity of tricuspid regurgitation. In 50 patients who underwent cardiac operations, 5 ml of dextrose or saline was injected into the right ventricle to generate echogenic "contrast." In patients with tricuspid regurgitation, there was systolic reflux of contrast into the right atrium, which could be semiquantified on a scale of 0 to 4+. Besides correlating well with preoperative Doppler studies for the presence or absence of tricuspid regurgitation in 18 patients (sensitivity = 0.90, specificity = 1.00), the intraoperative contrast method could quantify the severity of reflux. The 50 patients were divided into two groups on the basis of severity of tricuspid regurgitation as assessed by intraoperative two-dimensional contrast echocardiography. Group I (36 patients) had no or mild (0-2+) regurgitation, and Group II (14 patients) had moderate to severe (3-4+) tricuspid regurgitation. Patients with significant tricuspid regurgitation (Group II) had greater intraoperative preprocedure and postprocedure systolic and diastolic pulmonary pressures. Additionally, the systolic tricuspid anulus length, as measured in the intraoperative right ventricular inflow view, correlated better with severity of tricuspid regurgitation (r = 0.76, p = 0.005) than mean pulmonary pressure (r = 0.52, p less than 0.01). Therefore, intraoperative contrast two-dimensional echocardiography can accurately assess the relative severity of tricuspid regurgitation. Importantly, intraoperative measurement of tricuspid anulus diameter could predict the presence of significant echocardiographic tricuspid regurgitation before as well as immediately after the operation. Two-dimensional echocardiography may be an important intraoperative method both for evaluating the presence and severity of residual tricuspid regurgitation immediately after left heart operations as well as for determining which patients should undergo tricuspid valve repair.

Mitral valvuloplasty is superior to valve replacement for preservation of left ventricular function: an intraoperative two-dimensional echocardiographic study.

To investigate the mechanism and time of onset of ventricular dysfunction after mitral valve replacement, 18 patients with pure, severe mitral regurgitation (of whom 10 underwent mitral valve repair and 8 standard mitral valve replacement with papillary muscle excision) were studied by intraoperative two-dimensional echocardiography immediately before and immediately after the operative procedure. No patient sustained a perioperative myocardial infarction or had any residual mitral regurgitation. Although preoperative hemodynamics were similar, postoperatively the patients with valve repair had a lower pulmonary capillary wedge pressure than did the patients with valve replacement (8.6 +/- 1.9 versus 14.4 +/- 7.5 mm Hg, p less than 0.04). Although intraoperative echocardiographic ejection fraction fell significantly after mitral valve replacement (0.64 +/- 0.11 to 0.40 +/- 0.09, p less than 0.0001), it was maintained after valve repair (0.44 +/- 0.20 to 0.49 +/- 0.16, p = NS). Additionally, regional myocardial contractile abnormalities in the anterior and posterior septum were detected immediately after the procedure by intraoperative echocardiography in the patients with valve replacement, but not in those with repair. These postoperative regional contractile abnormalities after papillary muscle resection have not been described previously. Resection of the papillary muscles may disrupt the muscle bundle alignment and induce contractile abnormalities remote from the excised muscle. This study demonstrated that significant global and regional ventricular dysfunction develops immediately after removal of the papillary muscles, whereas myocardial contractility is preserved in patients undergoing mitral valve repair. Therefore, with intraoperative echocardiography to assure minimal residual regurgitation, surgeons should attempt to preserve ventricular function by performing mitral valve reconstruction in patients with mitral regurgitation.

Improved surgical approach to cardiac tumors with intraoperative two-dimensional echocardiography.

Intraoperative two-dimensional echocardiography allows visualization of cardiac anatomy and function not possible by other techniques. Although preoperative evaluation by noninvasive methods is usually adequate for diagnosis of cardiac tumors, two-dimensional echocardiography can be beneficial intraoperatively. Intraoperative echocardiography provides an accurate evaluation of cardiac anatomy, extent of tumor invasion, valvular function and the possible presence of intracardiac communications. Importantly, following tumor resection and a complex operative reconstructive procedure, the echocardiogram can confirm complete intracardiac tumor excision, evaluate post-repair ventricular function, and exclude an intracardiac communication or valvular insufficiency.

Aortic valvuloplasty for acquired aortic stenosis.

With the advent of reliable prosthetic valves, the number of aortic valvuloplastic procedures performed in adults has decreased significantly. This is in contradistinction to patients with congenital aortic stenosis, in whom aortic valvuloplasty remains the primary approach. Although only a 25% to 50% incidence of long-term clinical improvement has been reported after aortic valvuloplasty for acquired aortic stenosis, long-term success in adults can be predicted only if a valve area of greater than 1.0 cm2 is obtained, and if there is only minimal residual aortic insufficiency. Due to potential prosthetic valve-related complications aortic valvuloplasty was performed in 23 patients (14 women; nine men) with a mean age of 75 years (range 59 to 94). All patients had small aortic roots (20 less than or equal to 19 mm, 3 less than or equal to 21 mm) and a contraindication to anticoagulation. Baseline and postprocedure intraoperative two-dimensional contrast echocardiography was used to image leaflet mobility and the degree of aortic insufficiency. Cardiac outputs and pressure gradients were also recorded to calculate valve area before and after cardiopulmonary bypass. The postrepair gradient (mean 9 +/- 1.4 mm Hg) was significantly less (p = 0) than the prerepair gradient (mean 54 +/- 6.3 mm Hg). The postrepair valve area (mean 1.56 +/- 0.05 cm2) was significantly greater (p = 0) than the prerepair valve area (mean 0.55 +/- 0.05 cm2). Two patients required late reoperation: one for late bacterial endocarditis and one, whose valve area after valvuloplasty increased from 0.71 to only 0.91 cm2, for "restenosis."(ABSTRACT TRUNCATED AT 250 WORDS)

Intraoperative echocardiography for the evaluation of valvular regurgitation: experience in 263 patients.

Because of the limited orifice size and potential complications associated with prosthetic valves, native valve repair and reconstruction is an attractive surgical alternative. However, significant residual valvular regurgitation, which cannot be reliably detected intraoperatively by current methods, increases postoperative morbidity and mortality. Direct epicardial two-dimensional echocardiography with contrast injections can be applied intraoperatively to rapidly and accurately assess the presence and severity of valvular regurgitation in the baseline and postoperative state. Five milliliters of dextrose or saline are injected into the appropriate cardiac chamber, generating echogenic microbubbles (contrast) that normally exit in an antegrade direction, but reflux retrograde in the presence of valvular regurgitation. In a total of 263 patients who underwent intraoperative contrast echocardiography, 177 mitral, aortic, and tricuspid valves were adequately assessed by preoperative catheterization and results were compared with those of intraoperative contrast echocardiography. The sensitivity and specificity of the intraoperative detection of valvular regurgitation by echocardiography were 0.97 and 0.98, respectively, for all valves, 1.00 and 0.90 for mitral valves, and 0.91 and 1.00 for aortic valves. Moreover, intraoperative contrast echocardiography can also provide quantification of valvular regurgitation. In 120 mitral valves evaluated, the correlation between the degree of regurgitation determined by preoperative ventriculography and by intraoperative contrast echocardiography (both on a scale of 0 to 4+) was 0.93. Importantly, 11 patients who had mitral surgery (eight after mitral valve repair, and three after valve replacement) were identified as having significant postprocedure mitral regurgitation by intraoperative contrast echocardiography only, not by other methods. Additionally, nine patients were found to have significant tricuspid regurgitation by intraoperative contrast echocardiography after mitral surgery and underwent successful tricuspid annuloplasty.(ABSTRACT TRUNCATED AT 250 WORDS)

Localization of aortic dissection intimal flap by intraoperative two-dimensional echocardiography.

Ascending (type I) aortic dissection carries a high morbidity and mortality. Proper identification of the proximal origin of the dissection and determination of concomitant aortic valve involvement significantly facilitate surgical repair, which may improve survival. In this case, intraoperative two-dimensional echocardiography with contrast injections was used to image the heart and great vessels before and after cardiopulmonary bypass. The proximal origin of the intimal flap of a type I dissection was identified, and primary aortic valve disease was excluded. Postprocedure intraoperative echocardiography demonstrated that the site of repair was imaged and that aortic regurgitation was absent. Intraoperative contrast two-dimensional echocardiography may be a valuable new tool to provide information otherwise unavailable by routine techniques.