Etanercept therapy in patients with advanced primary amyloidosis.

No effective treatment exists for primary amyloidosis, a plasma cell dyscrasia characterized by deposition of amyloid fibrils consisting of monoclonal light chains in various organs. TNF-alpha has been implicated in other amyloid disorders; therefore, we used etanercept to treat patients with advanced amyloidosis who had failed other therapies or were ineligible for other treatment regimens. Sixteen patients with amyloidosis that included patients with severe cardiac or multiple organ involvement were treated with etanercept and evaluated every 4-6 wk for evidence of toxicity and clinical response. Patients were treated with etanercept for a median of 42 wk. Eight of 16 patients (50%) experienced objective improvements and 14 patients (88%) experienced subjective improvements in symptoms. Only one patient experienced an adverse effect attributable to etanercept. For the entire group, improvement in performance status was statistically significant (p = 0.001), estimated median survival is 24.2 mo, 8 of whom are still alive with a median survival is 26.6 mo. The 12 patients with any cardiac involvement had an estimated median survival of 24.2 mo. Six of those 12 patients are still alive, with a median survival is 26.6 mo. The group of eight patients with severe cardiac involvement showed an estimated median survival of 13.2 mo, three of whom are still alive with a median survival is 25.9 mo. The clinical observations in this group of advanced and relapsed/refractory patients are highly encouraging. For the group as a whole, median survival was 24.2 mo and improvement in performance status was highly significant. Median survival for the patients with severe cardiac involvement was 13.2 mo with 3/8 patients are alive with a median survival of 25+ mo. Moreover, there was a statistically significant improvement in patients' performance status. These results, even though in a small group of patients, suggest that etanercept may provide a new therapeutic option for the management of amyloidosis that should be studied further.

Cardiac exercise hemodynamics late after partial left ventriculectomy.

BACKGROUND: Although some patients report favorable activity levels late after partial left ventriculectomy (PLV), their exercise physiology has not been well described. METHODS AND RESULTS: We performed upright bicycle hemodynamics in 10 patients (9 men) aged 56+/-12 years at 1.7 years after PLV. Ejection fraction was 25+/-4%. Patients biked 10+/-7 minutes. With exercise, the mean pulmonary arterial pressure rose from 36+/-12 to 52+/-10 mm Hg (P:=0.0003). The mean pulmonary capillary wedge pressure rose from 25+/-14 to 36+/-9 mm Hg (P:=0.0566), and the cardiac index rose from 2.2+/-0.5 to 3.8+/-1.6 L. min(-1). m(-2) (P:=0.0077). The mixed venous oxygenation with exercise declined from 44+/-9% to 24+/-17% (P:=0. 0220), and the pulmonary vascular resistance increased from 2.0+/-0. 9 to 2.3+/-1.1 Wood units (P:=0.5566). CONCLUSIONS: In late follow-up after PLV with exercise, the cardiac index is significantly augmented. However, there are further rises in pulmonary artery and pulmonary capillary wedge pressures, suggesting abnormal compliance, with marked decline in mixed venous oxygenation. Elucidating late physiology after PLV may help pave the way for future innovative heart failure surgeries.

Exercise hemodynamic findings in patients with exertional dyspnea.

To determine whether upright bicycle exercise could provide useful information about disabling exertional dyspnea in the absence of severe abnormalities (as shown by traditional testing methods), we evaluated 13 such patients. There were 3 men and 10 women with a mean age of 49+/-15 (SD) years. We used pulmonary artery catheterization at rest and during upright bicycle exercise to evaluate these patients. All patients had normal left ventricular function except for 1, who had an ejection fraction of 45%. The mean duration to peak exercise was 9+/-6 minutes. Normal systolic pulmonary artery pressure was defined as 25+/-5 mmHg. Four patients had normal systolic pulmonary pressure, and 9 exhibited pulmonary hypertension with exercise. In those 9, the mean mixed pulmonary venous oxygen saturation at rest was 61%+/-9% and fell to 32%+/-9% at peak exercise. Six of the 9 patients also had some degree of resting pulmonary hypertension that worsened with exercise: their mean pulmonary artery systolic pressure at rest was 47+/-14 mmHg and rose to 75+/-25 mmHg at peak exertion (P = 0.01). The other 3 patients showed no pulmonary hypertension at rest; their mean pulmonary artery systolic pressure was 27+/-6 mmHg. However, this level rose to 53+/-4 mmHg at peak exertion (P = 0.04). In this pilot study of patients with dyspnea, 9 of 13 (69%) displayed marked pulmonary hypertension with exercise. The resting hemodynamic levels were normal in 3 (33%) of those with exercise pulmonary hypertension. We conclude that hemodynamic data from bicycle exercise tests can provide additional information regarding the mechanisms of exertional dyspnea.

Central nervous system plasticity after spinal cord injury in man: interlimb reflexes and the influence of cutaneous stimulation.

In persons who have sustained severe injuries to the cervical spinal cord, electrical stimulation of mixed peripheral nerves in a lower limb can evoke short-latency, bilateral motor responses in muscles of the distal upper limbs; such motor responses have been termed interlimb reflexes. In the present study, we investigated the role that cutaneous stimulation plays in evoking interlimb reflexes. Fifteen subjects with chronic injury (> 1 year) to the cervical spinal cord were investigated. Single motor unit activity was recorded from a number of distal upper limb muscles. The lower limb cutaneous area within which stimulation recruited a given motor unit of the upper limb was defined as that motor unit's 'receptive field'. Activity from a total of 48 single motor units was analyzed. The majority of motor units responded to light touch, individual hair movement, and thermal (hot and cold) stimulation. Excitatory responses were observed bilaterally, although contralateral responses predominated. Stimulation occasionally resulted in inhibition of a spontaneously active motor unit. Receptive fields varied a great deal in size, with proximal locations being larger than those encountered in more distal lower limb locations (i.e. the toes). The spinocervical tract is a possible candidate for mediating some portion of these interlimb reflexes, the origin of which may be due to new growth (regenerative sprouting) in the spinal cord caudal to a severe injury.