Increased plasma and renal clearance of an exchangeable pool of apolipoprotein A-I in subjects with low levels of high density lipoprotein cholesterol.

Plasma levels of HDL apo A-I are reduced in individuals with low HDL cholesterol (HDL-C) concentrations as a result of increased fractional catabolic rates (FCRs). To determine the basis for the high apo A-I FCRs, seven subjects with low HDL-C levels (31.0 +/- 4.3 mg/dl) were compared with three subjects with high HDL-C levels (72.0 +/- 4.5 mg/dl). Each subject received autologous HDL that was labeled directly by the iodine-monochloride method (whole-labeled) and autologous HDL that was labeled by exchange with homologous radiolabeled apo A-I (exchange-labeled). Blood was obtained for 2 wk, specific activities determined, and FCRs (d-1 +/- SD) estimated. In every subject, whether in the low or high HDL-C group, the exchange-labeled FCR was greater than the whole-labeled FCR. The exchange-labeled FCR was higher in the low HDL-C group (0.339 +/- 0.043) versus the high HDL-C group (0.234 +/- 0.047; P < 0.009). The whole-labeled FCR was also greater in the low HDL-C group (0.239 +/- 0.023) versus the high HDL-C group (0.161 +/- 0.064; P < 0.02). In addition, in both low and high HDL groups ultracentrifugation resulted in more radioactivity in d > 1.210 (as percentage of total plasma counts per minute) with the exchange-labeled tracer than with the whole-labeled tracer (12.55 +/- 4.95% vs. 1.02 +/- 0.38%; P < 0.003). With both HDL tracers, more radioactivity was found in d > 1.210 in the low versus the high HDL-C groups. When apo A-I catabolism was studied by perfusing isolated rabbit kidneys with whole-labeled HDL, there was twice as much accumulation (cpm/g cortex) of HDL apo A-I isolated from subjects with low HDL-C than from subjects with high HDL-C (P < 0.0025). Finally, HDL that had been isolated from subjects with high levels of HDL-C was triglyceride enriched and exposed to partially purified lipases before perfusion through kidneys. Threefold more apo A-I from modified HDL accumulated in the cortex compared with the unmodified preparation (P < 0.007). The results of these in vivo and ex vivo studies indicate that individuals with low HDL-C levels have more loosely bound, easily exchanged apo A-I and that this exchangeable apo A-I is more readily cleared by the kidney.

Role of brachytherapy in the management of pulmonary and mediastinal malignancies.

Brachytherapy, the permanent or temporary implantation of radioactive sources, has been performed in limited numbers of patients with lung cancer over the last 50 years. Because of renewed interest in this modality, we reviewed our experience with 103 patients treated over a 7-year period. The mean age of this group was 55.5 years (range, 1 to 84 years). Primary lung cancer accounted for 82 patients (79.6%); metastatic lesions to the lung, 13 (12.6%); and mediastinal malignancies, 8 (7.8%). Indications for brachytherapy included mediastinal and chest wall invasion in 42 patients (40.8%), unresectable tumors and mediastinal adenopathy in 30 (29.1%), medical contraindications to extensive pulmonary resection in 20 (19.4%), and irradiation of excised lymph node beds in 11 (10.7%). Seeds labeled with radioactive iodine 125 alone were used in 65 patients (63.1%), afterloading catheters containing iridium 192 sources in 25 (24.3%), and both in 13 (12.6%). There were no operative deaths. With a mean follow-up of 18.6 months, the mean and median survivals for the entire group were 17.3 and 14.0 months, respectively. The 1-year, 2-year, and 3-year survivals for the entire group were 67.9%, 38.7%, and 27.8%, respectively. In summary, brachytherapy offers a useful surgical approach in patients in whom unresectable pulmonary or mediastinal malignancies are found at the time of thoracotomy or in patients previously treated with other modalities for whom limited therapeutic alternatives exist.