Tetanus toxin fragment C as a vector to enhance delivery of proteins to the CNS.

The non-toxic neuronal binding domain of tetanus toxin (tetanus toxin fragment C, TTC) has been used as a vector to enhance delivery of potentially therapeutic proteins to motor neurons from the periphery following an intramuscular injection. The unique binding and transport properties of this 50-kDa polypeptide suggest that it might also enhance delivery of proteins to neurons after direct injection into the CNS. Using quantitative fluorimetry, we found that labeled TTC showed vastly superior retention within brain tissue after intracerebral injection compared to a control protein (bovine serum album). Fluorescence microscopy revealed that injected TTC was not retained solely in a restricted deposit along the needle track, but was distributed through gray matter in a pattern not previously described. The distribution of injected protein within the extracellular space of the gray matter and neuropil was also seen after injection of a recombinant fusion protein comprised of TTC linked to the enzyme superoxide dismutase (TTC-SOD-1). Injections of native SOD-1 in contrast showed only minimal retention of protein along the injection track. Immunohistochemistry demonstrated that both TTC and TTC-SOD-1 were distributed in a punctate perineuronal and intraneuronal pattern similar to that seen after their retrograde transport, suggesting localization primarily in synaptic boutons. This synaptic distribution was confirmed using HRP-labeled TTC with electron microscopy along with localization within neuronal endosomes. We conclude that TTC may be a useful vector to enhance neuronal delivery of potentially therapeutic enzymes or trophic factors following direct injection into the brain.

Atrial ejection force in patients with atrial fibrillation: comparison between DC shock and pharmacological cardioversion.

It is well known that the restoration of sinus rhythm is not always associated with the return of effective atrial contraction. Atrial ejection force (AEF) is a noninvasive Doppler derived parameter that measures the strength of the atrial contraction. The aim of the present study was to use pulsed-Doppler echocardiography to determine if different modalities of cardioversion influence the delay in the return of effective atrial contraction after cardioversion. DC shock and pharmacological therapy were compared. Sixty-eight patients were randomly cardioverted, either using DC shock or i.v. procainamide. The patients who were restored to a sinus rhythm had a complete Doppler echocardiographic examination within 1 hour after the restoration, after 24 hours, after 1 month, and after 3 months. AEF was measured and compared in the two groups of patients and within the same group. AEF was greater immediately and at 24 hours after cardioversion in patients who underwent pharmacological therapy compared to patients treated with DC shock (peak A wave, 60 +/- 9 vs 31 +/- 8 msec, P < 0.001; AEF 11.3 +/- 3 vs 5 +/- 2.9 dynes, P < 0.001). In both groups, AEF increases over time. In conclusion, AEF is a noninvasive parameter that can be easily measured after cardioversion and can give accurate information about the recovery of left atrial mechanical function. This finding may have important implications for guiding the anticoagulant therapy after cardioversion.

Doppler echocardiographic findings in patients with right ventricular infarction.

Doppler Echocardiographic Findings in Patients with Right Ventricular Infarction Transthoracic Doppler echocardiography was performed in 96 consecutive patients with right ventricular infarction treated with thrombolysis. The bedside examination was performed before and 2 to 3 hours after thrombolytic therapy, and a subsequent follow-up examination was scheduled for 7 days later. The in-hospital and long-term course was determined for all patients. Significant differences were found in echocardiographic findings after the thrombolytic therapy: the right ventricular diameter decreased from 28.8 mm+/-5.8 to 22.5 mm +/- 4.3 (P < 0.001), tricuspid regurgitant flow peak velocity was reduced from 2.9 m/s +/- 0.3 to 2.0 m/s +/- 0.5 (P < 0.001). The analysis of interatrial septal motion and interventricular septal motion showed a normalization in many patients. Major complications and deaths were more frequent in patients with echocardiographic findings of pulmonary hypertension persisting after thrombolytic therapy. Echocardiographic findings involving the right side of the heart are frequent in patients with right ventricular infarction. The presence of a severe tricuspid regurgitation and of an abnormal septal motion in patients with acute myocardial infarction indicates involvement of the right ventricle.

Doppler echocardiographic parameters predictive of recurrence of atrial fibrillation of different etiologic origins.

Atrial fibrillation is a common arrhythmia associated with an increased risk for the occurrence of embolism. Recurrences of atrial fibrillation are very frequent and increase the risk for an embolic event. The aim of the present study was to identify the clinical and echocardiographic parameters that are predictive of the recurrence of atrial fibrillation. One hundred and twenty consecutive patients with non-rheumatic atrial fibrillation were followed for 1 year after cardioversion. The following parameters were evaluated: cause and duration of atrial fibrillation, modality of cardioversion, atrial function after cardioversion (peak A wave velocity and A wave integral), left atrial dimension, peak E wave velocity of the transmitral inflow pattern, acceleration and deceleration times, and the integral of E wave. At 1 year, 72 patients maintained sinus rhythm whereas 48 patients had a recurrence of atrial fibrillation. The univariate analysis revealed that the parameter with the strongest influence on the recurrence of atrial fibrillation was the peak A velocity after cardioversion (P < 0.001). The other parameters associated with recurrences were cause of atrial fibrillation (P < 0.001), duration of arrhythmia (P = 0.002), and left atrial dimension (P = 0.05). The modality of cardioversion and the E wave variables did not influence the recurrence of atrial fibrillation. The peak A velocity was smaller in the group of patients who had a recurrence. We suggest that clinical and echocardiographic parameters, such as A wave variables, be used to identify patients at risk for recurrence. These patients should be monitored more frequently and should eventually be treated with antiarrhythmic drugs.