Phase II trial of liposomal daunorubicin in the treatment of AIDS-related pulmonary Kaposi's sarcoma.

PURPOSE: Kaposi's sarcoma (KS) is the most common tumor in patients with AIDS and can be fatal in patients with lung involvement. Systemic chemotherapy is the most effective treatment for pulmonary KS. We thus conducted this study to determine the efficacy of liposomal daunorubicin in the treatment of patients with pulmonary KS. METHODS: Patients with biopsy-proven, symptomatic pulmonary KS were accrued. Liposomal daunorubicin was given at a dose of 60 mg/m2 intravenously every 2 weeks. Response was monitored by chest radiographs, pulmonary function tests, arterial blood gases, and grading of pulmonary symptoms. RESULTS: Fifty-three male patients were accrued. The median CD4+ lymphocyte count was 13/microL (range, 0 to 200); 70% reported a prior AIDS-defining opportunistic infection. All patients were symptomatic, with cough reported in all patients, shortness of breath in 94%, and hemoptysis in 55%. The mean study entry diffusing capacity of carbon monoxide (DLCO) was 58.5% (percent of predicted). The median dose of liposomal daunorubicin delivered was 360 mg/m2 (range, 60 to 1,380). More than 75% of patients had complete or partial resolution of baseline pulmonary symptoms. Complete or partial improvement in DLCO was observed in 22%; complete or partial resolution of radiographic abnormalities was reported in 32%. The most common treatment-related toxicity was neutropenia, which occurred in 85%. There were no instances of cardiac toxicity observed, even at high cumulative doses. CONCLUSION: Liposomal daunorubicin at 60 mg/m2 is safe and active in patients with pulmonary KS. Trials combining liposomal daunorubicin with other active agents in KS should be considered.

Upper and middle lobe bronchoalveolar lavage to diagnose Pneumocystis carinii pneumonia.

Pneumocystis carinii pneumonia (PCP) remains the most common lethal opportunistic pulmonary infection in patients infected with the human immunodeficiency virus (HIV). Although the use of prophylactic inhaled pentamidine has effectively reduced the frequency of primary and recurrent episodes of PCP, the aerosolization of pentamidine may have altered the localization of active PCP, resulting in more upper lobe disease. The distribution of disease may have also affected the diagnostic accuracy of standard bronchoalveolar lavage of the middle lobe, with a reduction in sensitivity from about 90 to 65%. In retrospective surveys of patients from our institution, Steiger and Fahy found that pooled multiple-lobe radiographic site-directed bronchoalveolar lavage resulted in diagnostic sensitivities of 91 and 100%, respectively. We performed a follow-up prospective study of 38 consecutive patients on aerosolized pentamidine in whom we lavaged both the middle lobe and an upper lobe. We found that bilobar lavage including routine lavage of an upper lobe increases the diagnostic sensitivity of bronchoalveolar lavage alone to 95% compared with 65% if lavage is performed only in the middle lobe (p < 0.05). Radiographic studies demonstrate a concordant increase in exclusive or predominant upper lobe disease in patients on aerosolized pentamidine, but our results indicate that PCP is recovered more frequently from the upper lobe regardless of the radiographic appearance. We conclude that all patients on prophylactic inhaled pentamidine should undergo bilobar lavage with the inclusion of an upper lobe in the initial evaluation of possible PCP. The diagnostic sensitivity of 95% makes bilobar bronchoalveolar lavage an acceptable sole initial diagnostic modality without the need for initial transbronchial lung biopsy.

Separation and partial purification of acid phosphates of the enamel organ of rat molars.

At least two types of acid phosphatases with markedly different properties were separated from the enamel organ of rat molar tooth buds. One enzyme (A) bound weakly to the CM-cellulose column and was eluted with a combined linear salt and pH gradient; another enzyme (B) bound strongly to the column and was eluted with a second linear salt gradient at constant pH. Enzyme A was identified as a phosphomonoester hydrolase (3.1.3.2) similar to the lysosomal enzyme of soft tissues and the tartrate-sensitive enzyme of bone. Enzyme B did not hydrolyse aliphatic monophosphate ester substrates but, like enzyme A, it did split the aryl monophosphate ester substrate, para-nitrophenylphosphate, as well as the phosphate esters of casein and the acid anhydride substrates, ATP and inorganic pyrophosphate. This enzyme is similar to the low molecular weight tartrate-resistant acid phosphatases of bone and soft tissues.