Citations

PURPOSE: Yttrium-90 (90Y) ibritumomab tiuxetan (Zevalin; IDEC Pharmaceutical, San Diego, CA) is an effective therapy for patients with relapsed B-cell non-Hodgkin’s lymphoma. The predominant toxicity of90Y ibritumomab tiuxetan has been myelosuppression, and concern has been expressed about the tolerability of further treatment after this therapy. The goal of this analysis was to evaluate the therapy given to patients who relapsed after90Y ibritumomab tiuxetan.PATIENTS AND METHODS: A retrospective analysis was performed on 58 patients treated at a single institution on five separate protocols that used90Y ibritumomab tiuxetan 0.4 mCi/kg. All patients had experienced disease progression after90Y ibritumomab tiuxetan treatment and received subsequent therapy. The toxicity seen in this cohort of patients with subsequent treatment regimens was analyzed and compared with that of control groups who did not receive90Y ibritumomab tiuxetan.RESULTS: The median number of subsequent therapies was two (range, one to seven). Sixteen (28%) of the 58 patients received growth factor support with subsequent chemotherapy, and two patients were treated with reduced doses because of persistent pancytopenia. Eight patients subsequently had an autologous stem-cell transplantation with stem cells collected after90Y ibritumomab tiuxetan therapy. Excluding patients hospitalized at the time of transplantation, 13 patients were hospitalized for neutropenic fever, thrombocytopenia, or both. When compared to patients who did not receive90Y ibritumomab tiuxetan, there was no significant difference in toxicity.CONCLUSION: We conclude that chemotherapy or autologous stem-cell transplantation after prior therapy with90Y ibritumomab tiuxetan is feasible and reasonably well tolerated. The toxicity with subsequent therapy seems similar to that in patients not treated with90Y ibritumomab tiuxetan.

Background— Muscle sympathetic vasoconstrictor nerve activity increases with age in healthy humans but does not result in an augmented forearm vasoconstrictor tone. We tested the hypothesis that this is due to a reduction in postjunctional α-adrenergic responsiveness to endogenous norepinephrine (NE) release and determined whether this was specific to α 1 - or α 2 -adrenergic receptors. Methods and Results— Forearm blood flow (FBF, by strain-gauge plethysmography) responses to local intra-arterial infusions of tyramine (which evokes endogenous NE release), phenylephrine (selective α 1 -agonist), and clonidine (α 2 -agonist) were determined in 10 young (aged 26±1 [mean±SEM] years) and 10 older (aged 65±1 years) healthy normotensive men after local β-adrenergic blockade with propranolol. Basal forearm vascular tone was not different in young men and older men. The percentage reduction in FBF in response to the highest dose of tyramine was blunted in older men compared with young men (−37±3% versus −49±3%, respectively; P <0.01) despite a greater increase in deep venous NE concentration in older men (910±103 versus 565±69 pg/mL, respectively; P <0.001). Maximal reductions in FBF to phenylephrine were also blunted in older men (−47±2% versus −58±3% in young men, P <0.05). In contrast, the reductions in FBF (−36±7% versus −40±3% for older versus young men, respectively) and also in venous NE concentration (−79±24 versus −84±13 pg/mL for older versus young men, respectively) to clonidine were similar in the 2 groups. Finally, forearm sympathetic α-adrenergic vasoconstrictor tone (assessed via nonselective α-blockade with phentolamine) was significantly lower in older men. Conclusions— Our results indicate that human aging is associated with a reduction in forearm postjunctional α-adrenergic responsiveness to endogenous NE release and that this might be specific to α 1 -adrenergic receptors. Furthermore, the contribution of sympathetic α-adrenergic vasoconstriction to basal forearm vascular tone is reduced with age in healthy men.

Background— The outcome of mitral valve prolapse (MVP) is controversial, with marked discrepancies in reported complication rates. Methods and Results— We conducted a community study of all Olmsted County, Minn, residents first diagnosed with asymptomatic MVP between 1989 and 1998 (N=833). Diagnosis, motivated by auscultatory findings (n=557) or incidental (n=276), was always confirmed by echocardiography with the use of current criteria. End points analyzed during 4581 person-years of follow-up were mortality (n=96, 19±2% at 10 years), cardiovascular morbidity (n=171), and MVP-related events (n=109, 20±2% at 10 years). The most frequent primary risk factors for cardiovascular mortality were mitral regurgitation from moderate to severe ( P =0.002, n=131) and, less frequently, ejection fraction <50% ( P =0.003, n=31). Secondary risk factors independently predictive of cardiovascular morbidity were slight mitral regurgitation, left atrium ≥40 mm, flail leaflet, atrial fibrillation, and age ≥50 years (all P <0.01). Patients with only 0 or 1 secondary risk factor (n=430) had excellent outcome, with 10-year mortality of 5±2% ( P =0.17 versus expected), cardiovascular morbidity of 0.5%/y, and MVP-related events of 0.2%/y. Patients with ≥2 secondary risk factors (n=250) had mortality similar to expected ( P =0.20) but high cardiovascular morbidity (6.2%/y, P <0.01) and notable MVP-related events (1.7%/y, P <0.01). Patients with primary risk factors (n=153) showed excess 10-year mortality (45±9%, P =0.01 versus expected), high morbidity (18.5%/y, P <0.01), and high MVP-related events (15%/y, P <0.01). Conclusions— Natural history of asymptomatic MVP in the community is widely heterogeneous and may be severe. Clinical and echocardiographic characteristics allow separation of the majority of patients with excellent prognosis from subsets of patients displaying, during follow-up, high morbidity or even excess mortality as direct a consequence of MVP.

A quantitative model is presented for a sphere vibrated by two ultrasound beams of frequency ω1 and ω2. Due to the interference of two sound beams, the radiation force has a dynamic component of frequency ω2−ω1. The radiation impedance and mechanical impedance of the sphere are then used to compute the vibration speed of the sphere. Vibration speed versus vibration frequency is measured by laser vibrometer on several spheres, both in water and in gel phantom. These experimental results are used to verify the model. This method can be used to estimate the material properties of the medium (e.g., shear modulus) surrounding the sphere.