Transgenic models to assess the pathogenic actions of cytokines in the central nervous system.

In order to better understand the actions of proinflammatory cytokines in the mammalian CNS, a transgenic approach was employed in which the expression of IL-6, IL-3 or TNF-alpha was targeted to astrocytes in the intact CNS of mice. Transgenic mice exhibited distinct chronic-progressive neurological disorders with neurodegeneration and cognitive decline due to IL-6 expression, macrophage/microglial-mediated primary demyelination with motor impairment due to IL-3 expression and lymphocytic meningoencephalomyelitis with paralysis induced by TNF-alpha expression. Thus, expression of specific cytokines alone in the intact CNS results in unique neuropathological alterations and functional impairments, thereby directly implicating these mediators in the pathogenesis of CNS disease.

Comparative effects of the combination of digoxin and dl-sotalol therapy versus digoxin monotherapy for control of ventricular response in chronic atrial fibrillation. dl-Sotalol Atrial Fibrillation Study Group.

To establish the value of adjuvant dl-sotalol to digoxin for control of the ventricular response in chronic atrial fibrillation, 60 patients were evaluated in a multicenter, randomized, double-blind, parallel, placebo-controlled study. Patients were evaluated with serial ambulatory ECG monitoring and exercise testing during stable digoxin dosing and then with the addition of either a placebo or dl-sotalol, 80 mg/day, or dl-sotalol, 160 mg/day. The combination of digoxin and dl-sotalol, at either 80 or 160 mg/day, resulted in a statistically significant reduction in heart rate at rest and with exercise during both exercise testing and ambulatory monitoring. No significant difference was observed between the two doses of dl-sotalol. There was no significant difference with regard to symptoms or side effects among the three groups. In summary, dl-sotalol was noted to be a safe and effective adjuvant to digoxin for control of the ventricular response in chronic atrial fibrillation.

Experience with the use of tPA in the treatment of acute myocardial infarction.

Early experience with the use of tissue plasminogen activator (tPA) in acute myocardial infarction is reviewed, including comparisons with other thrombolytic agents, a summary of hemorrhagic complications associated with its use, and the rationale for adjunctive therapeutic strategies. The use of tPA has been associated with improvement in left ventricular function, a lower mortality, and a decrease in congestive heart failure signs and symptoms. A protocol for evaluation of patients with possible myocardial infarction for thrombolytic therapy is presented. Consideration must be given to other possible diagnoses, and the ECG must be evaluated carefully to ensure that appropriate criteria are met. Risk factors for hemorrhagic complications include recent trauma, surgery, gastrointestinal and genitourinary bleeding, stroke, and focal neurologic findings. Greater benefit of therapy is expected in patients with larger infarcts who have more marked ST segment changes or evidence of hemodynamic compromise, especially when they are treated early after the onset of symptoms (within the first several hours). Adjunctive measures that can be considered in the emergency department include prophylactic lidocaine, IV nitroglycerin, beta blockade, aspirin, volume replacement and monitoring for dysrhythmias, bleeding, and recurrent ischemia. A comprehensive understanding of these rapidly evolving concepts will assist the emergency physician in the evaluation and management of patients with acute myocardial infarction.

Helicopter transport of patients during acute myocardial infarction.

Initial experience with a regional system of emergency helicopter transport of patients with acute myocardial infarction (AMI) referred for emergent cardiac catheterization and percutaneous transluminal coronary angioplasty (PTCA) is described. Two hundred fifty patients with AMI were transported from within a 150-mile radius to Duke University Medical Center over a 15-month period. All patients were within 12 hours of onset of symptoms. Thrombolytic therapy was administered to 240 (96%) patients (72% before or in-flight). The time to administration of thrombolytic therapy ranged from 30 to 120 minutes (median 180), while the time to arrival in the interventional catheterization laboratory ranged from 105 to 815 minutes (median 300). The flight time was 12 to 77 minutes (median 31). Most patients had 1- or 2-vessel coronary artery disease; the baseline ejection fraction ranged from 27 to 70% (median 42). Transient hypotension was the most common complication both pre-flight and in-flight. Third-degree atrioventricular block and nonsustained ventricular tachycardia were the next most common complications. Ventricular fibrillation or sustained ventricular tachycardia occurred before takeoff in 38 patients (15%). No patients had ventricular fibrillation, asystole or respiratory arrest during transport. Fluid boluses for hypotension were the most common intervention. Five patients required cardiopulmonary resuscitation in-flight; 3 before lift-off and 2 required a brief period of cardiopulmonary resuscitation during sustained ventricular tachycardia. Fourteen patients had pressor therapy, military antishock trousers or both to maintain adequate blood pressure. Neither cardioversion, defibrillation nor intubation were performed in-flight. Thus, inflight complications are infrequent and can be managed en route to an intervention center.(ABSTRACT TRUNCATED AT 250 WORDS)

A review of pericarditis. 2. Specific pericardial disorders.

Pericardial disease encompasses a wide range of etiologies and manifestations, the most common of which have been described. Treatments include use of drug therapy, surgical drainage, pericardiectomy, and pericardiotomy. In most cases, treatment is effective.

A review of pericarditis. 1. Causes, manifestations, and diagnostic techniques.

Pericardial disease has many causes, clinical manifestations, and complications. Pericarditis, the most common disease of the pericardium, is classified as acute, subacute, or chronic. Acute pericarditis is characterized by chest pain, dyspnea, and presence of a pericardial friction rub. Patients with chronic pericarditis are generally asymptomatic. Laboratory techniques such as electrocardiography, echocardiography, angiography, radionuclide ventriculography, and computed tomography are useful as primary or adjunctive diagnostic procedures.

Sarcoidosis mimicking cor triatriatum. Echolucency of adenopathy due to sarcoidosis.

A 20-year-old man with sarcoidosis presented with the echocardiographic findings of cor triatriatum. Computed tomography of the chest and digital subtraction angiography of the heart revealed that the patient had massive retrocardiac lymphadenopathy and normal cardiac anatomy. This is the first report demonstrating the echolucency of sarcoid lymphadenopathy and the mimicking of cor triatriatum by such adenopathy fortuitously positioned.