Joan J Ryoo | PubMed Health

PubMed2005

Capnogram shape in obstructive lung disease.

Small, preliminary studies have suggested that capnograms of obstructive lung disease (OD) exhibit a characteristic shape and that this shape may be correlated to changes in forced expiratory volume in 1 s (FEV(1)). We evaluated the association between capnograms and spirometry from subjects with OD with normal and restrictive lung disease (RD) subjects. The study was conducted in a prospective, nonrandomized manner using a convenience sample of 262 subjects presenting to a pulmonary function laboratory. Capnograms were recorded before pulmonary function testing. Subjects with OD had capnograms that were significantly different from normal and RD subjects. These differences were progressive, increasing with disease severity. The average take-off angle of the ascending phase for severe OD was 7.2 degrees less (95% confidence interval [CI]: 4.0, 10.4) than for normals. The average alveolar plateau elevation angle was 0.8 degrees more (95% CI: 0.14, 1.4) for moderate OD than for normals, whereas the average elevation angle was 3.6 degrees more (95% CI: 2.9, 4.3) for severe OD than for normals. Differences between OD capnograms and normal and RD capnograms, correlating to changes in FEV(1), were sufficiently large enough to suggest that the capnogram could be used to discriminate between OD and normal.

Adult↗

PubMed2002

Immunomodulatory drug CC-5013 overcomes drug resistance and is well tolerated in patients with relapsed multiple myeloma.

Thalidomide (Thal) can overcome drug resistance in multiple myeloma (MM) but is associated with somnolence, constipation, and neuropathy. In previous in vitro studies, we have shown that the potent immunomodulatory derivative of thalidomide (IMiD) CC-5013 induces apoptosis or growth arrest even in resistant MM cell lines and patient cells, decreases binding of MM cells to bone marrow stromal cells (BMSCs), inhibits the production in the BM milieu of cytokines (interleukin-6 [IL-6], vascular endothelial growth factor [VEGF], tumor necrosis factor-alpha [TNF-alpha]) mediating growth and survival of MM cells, blocks angiogenesis, and stimulates host anti-MM natural killer (NK) cell immunity. Moreover, CC-5013 also inhibits tumor growth, decreases angiogenesis, and prolongs host survival in a human plasmacytoma mouse model. In the present study, we carried out a phase 1 CC-5013 dose-escalation (5 mg/d, 10 mg/d, 25 mg/d, and 50 mg/d) study in 27 patients (median age 57 years; range, 40-71 years) with relapsed and refractory relapsed MM. They received a median of 3 prior regimens (range, 2-6 regimens), including autologous stem cell transplantation and Thal in 15 and 16 patients, respectively. In 24 evaluable patients, no dose-limiting toxicity (DLT) was observed in patients treated at any dose level within the first 28 days; however, grade 3 myelosuppression developed after day 28 in all 13 patients treated with 50 mg/d CC-5013. In 12 patients, dose reduction to 25 mg/d was well tolerated and therefore considered the maximal tolerated dose (MTD). Importantly, no significant somnolence, constipation, or neuropathy has been seen in any cohort. Best responses of at least 25% reduction in paraprotein occurred in 17 (71%) of 24 patients (90% confidence interval [CI], 52%-85%), including 11 (46%) patients who had received prior Thal. Stable disease (less than 25% reduction in paraprotein) was observed in an additional 2 (8%) patients. Therefore, 17 (71%) of 24 patients (90% CI, 52%-85%) demonstrated benefit from treatment. Our study therefore provides the basis for the evaluation of CC-5013, either alone or in combination, to treat patients with MM at earlier stages of disease.

Adjuvants, Immunologic↗

PubMed2002

Novel therapies for multiple myeloma.

Multiple myeloma (MM) continues to evade cure by conventional therapies, increasing the urgency for new, biologically based treatments. Reviewed in this discussion are novel chemotherapies under clinical trial that capitalize upon greater comprehension of tumor pathophysiology. In targeting tumor biology, these therapies serve as a model of treatment with great potential for improving outcomes in patients with MM.

2-Methoxyestradiol↗