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Background: To explore the potential role of infiltrating benign B cells in classic Hodgkin disease (HD) lesions in supporting the survival of malignant Hodgkin and Reed-Sternberg (H/RS) cells, the authors initiated a pilot study of rituximab. Rituximab is used to primarily deplete normal B cells from HD lesions., Methods: Patients with recurrent, classic HD who had received a minimum of two prior treatment regimens, regardless of whether H/RS cells expressed CD20, were treated with 6 weekly doses of 375 mg/m2 rituximab to selectively deplete infiltrating benign B cells. Objective tumor response was determined 3 weeks after completion of the last dose of rituximab and every 3 months thereafter. Serum samples were collected from patients before they started rituximab therapy and 3 weeks after the final course of rituximab. Serum cytokine levels of interleukin 6 (IL-6), IL-10, IL-12, IL-13, and interferon gamma were determined using commercially available enzyme-linked immunosorbent assay kits., Results: Twenty-two patients with nodular sclerosis histology were evaluable for treatment response. Five patients (22%) achieved partial or complete remission that lasted for a median of 7.8 months (range, 3.3-14.9 months). Remissions were observed in patients only at lymph node and splenic sites, but not at extranodal sites, and were irrespective of CD20 expression by H/RS cells. Furthermore, systemic (B) symptoms resolved in six of seven patients after therapy. In two patients, partial remissions were associated with a decline in serum IL-6 levels., Conclusions: The current data suggest that rituximab therapy in patients with recurrent, classic HD can alter serum IL-6 cytokine levels, can improve B symptoms, and may result in clinical remissions., (Copyright 2003 American Cancer Society.)

Pharmacodynamic effects of combination therapy with omapatrilat and furosemide were evaluated. Two groups of 13 healthy subjects each received furosemide 20 mg dailyfor 15 days coadministered with either placebo on days 6 to 15 or omapatrilat 10 mg on days 6 to 10 and 25 mg on days 11 to 15. In the omapatrilat group, urinary excretion of atrial natriuretic peptide increased, and greater blood pressure reductions were seen compared with placebo. Concomitant omapatrilat treatment did not affect the acute diuresis, natriuresis, and kaliuresis observed with chronic administration of furosemide. Neither effective renal plasma flow nor glomerularfiltration rate changed in either treatment group. No clinically significant safety issues were observed. Daily coadministration of omapatrilat 10 or 25 mg with furosemide 20 mg does not affect the pharmacodynamics offurosemide at steady state.

The purpose of this study was to determine the pharmacodynamics and pharmacokinetics of omapatrilat, administered orally (25 mg) or intravenously (10 mg) in 19 New York Heart Association class II and class III congestive heart failure (CHF) patients versus 17 healthy controls matched for age, race, gender, and weight. The plasma concentrations of atrial natriuretic peptide (ANP) increased by approximately 20% and 30% in CHF and control subjects, respectively, at 4 hours after intravenous or oral omapatrilat administration. Similar elevation in the cyclic guanosine monophosphate concentration (25% to 35%) and ANP urinary excretion (21 ng/24 h to 22 ng/24 h) was seen in all treatment groups after omapatrilat administration. Angiotensin-converting enzyme activity was > 90% inhibited at 4 hours after dosing and remained approximately 60% to 70% inhibited at 24 hours after dosing. The levels of endothelin-1 and endothelin-2 remained unchanged after oral or intravenous administration of omapatrilat. The maximal reduction in seated blood pressure compared with baseline was similarfor CHF and control subjects. Clinical pharmacokinetic parameters were similar in both groups after intravenous dosing, but maximum concentration and area under the concentration-time curve were elevated in CHF patients compared with controls after oral dosing. Omapatrilat was well tolerated; differences in systemic exposure and metabolism between CHF patients and controls did not appear to be clinically significant.

The effect of feast/famine growth conditions on activated sludge cultures indicates that nonfilamentous cultures can be selected by providing proper substrate gradients and extended periods of endogenous metablism. Reactor operating strategies providing intermittently high substrate concentrations result in cultures characterized by high peak substrate and oxygen uptake activities, rapid settling rates, and high resistance to starvation. Sludge settleability can be manipulated using controlled variations in growth environment with corresponding changes noted in sludge activity. In combination with the low net growth rates associated with activated sludge systems, feast/famine environments would logically convey a selection advantage to microbes capable of readily assimilating substrate materials and maintaining viability during extended starvation periods.

A review of the pathologic material from 34 patients having bronchioloalveolar carcinoma has demonstrated two histopathologic types that have a bearing on the prognosis. Type 1 is associated with gross and microscopic mucus production, and is likely to be multicentric. Type 2 has lesser amounts of mucus, and is likely to be solitary. The 5-year survival of type 1 is 26%, and that of type 2 is 72%.