CO concentration-dependent changes in pulmonary diffusing capacity in humans.

Steady-state CO pulmonary diffusing capacity (DLCO) was measured at different inspired CO concentrations in seven males and one female during light treadmill exercise. As the CO level is increased. DLCO increases, reaches a maximum at an end-tidal CO concentration of approximately 100 ppm, and then decreases. The maximum DLCO is up to twice as large as the DLCO measured at an inspired CO concentration of approximately 1,780 ppm. These results are consistent with the presence of saturation kinetics, one of the basic properties of carrier-mediated transport systems. A similar relationship between DLCO and CO concentration was found in previous studies of mechanically ventilated dogs. Thus there is evidence for carrier-mediated transport of CO in the lungs of both humans and dogs.

Effect of hypoxia and CO on a cytochrome P-450-mediated reaction in rabbit lungs.

Evidence indicates that the diffusion of O2 and CO in tissue may be facilitated by a carrier molecule having a P50 that approximates tissue O2 partial pressure (PO2; 1-15 Torr) and a much higher affinity for CO than for O2. To determine whether cytochrome P-450 in lung satisfies these criteria, we measured the effect of hypoxia and of CO on the rate of metabolism of the cytochrome P-450 mediated O-demethylation of p-nitroanisole in isolated perfused rabbit lungs. Metabolism was inhibited by 50% of a control at an estimated tissue PO2 fo 4 Torr (5.5 microM). When inspired CO2 was kept at 200 Torr and inspired CO partial pressure (PCO) varied an estimated tissue PCO/PO2 ratio of 0.025 reduced the reaction rate by 50% of control, but some metabolism persisted at PCO/PO2 ratios larger than one. The relationship between reaction rate and PCO/PO2 ratio could not be fit by a single value for Haldane constant for M (CO affinity/O2 affinity) but could be described with a two-component model in which metabolism was equally divided between a high-affinity cytochrome (M = 200) and a low-affinity cytochrome (M = 2). These findings suggest that cytochrome P-450 could act as a carrier for O2 and CO in tissue with low PO2's.

Human alveolar macrophages: antigen-independent binding of lymphocytes.

To characterize the initial step in alveolar macrophage (AM)-lymphocyte (L) interaction in the human lung, we studied the ability of human AM to bind autologous blood L in vitro in the absence of antigen. AM were obtained by saline bronchial lavage through a fiberoptic bronchoscope. Monolayers of AM attached to glass bound autologous blood L prepared by Ficoll-Hypaque and nylon wool column separation. The AM-L binding increased from zero time to a maximum at 2 h and then declined to a zero time value at 18 h. The binding was dependent on the number of L added to the AM monolayers, with greatest binding at an AM:L ratio of 1:50. AM:L binding required viability of AM, but not of L, and was temperature dependent. Pretreatment of AM with iodoacetic acid, trypsin, neuraminidase, or colchicine diminished attachment of L at 2 h. Neuraminidase pretreatment of L resulted in increased binding to nontreated AM. Thus, a physical interaction between human AM and autologous peripheral blood L can occur in vitro in the absence of known antigen; similar interaction in vivo may play a role in the generation of cell-mediated immune responses in the lung.

Granulomatous biliary tract obstruction due to sarcoidosis. Report of a case and review of the literature.

A 29-year-old woman with sarcoidosis developed obstructive jaundice due to granulomatous involvement of the common hepatic duct and surrounding lymph nodes. After temporary decompression by T-tube, obstruction was alleviated by corticosteroid therapy.

Tetracycline and quinacrine in the control of malignant pleural effusions. A randomized trial.

Eighteen patients with advanced metastatic malignancy who had 21 pleural effusions requiring sclerosis for control were randomly allocated to intrapleural therapy with tetracycline or quinacrine. Tetracycline produced partial or complete control of the effusion in ten of 12 trials for a median duration of 6 months (range 1.5 to 22 months). Partial or complete control was obtained in nine of ten trials with quinacrine, for a median duration of 3 months (range 1 to 13 months). All complete responders who died achieved control of their effusions until their terminal admissions despite clinical evidence of overt systemic tumor progression in the intervening period. Single-dose tetracycline therapy was accompanied by less fever (p less than 0.04) and less pleuritic pain (p = 0.09) than quinacrine. Tetracycline is effective, well tolerated, easily administered, and should be considered as the initial therapy for malignant pleural effusions requiring pleural sclerosis.

Sarcoidosis following adjuvant high-dose methotrexate therapy for osteosarcoma.

A patient who had undergone amputation and adjuvant chemotherapy with methotrexate doxorubicin hydrochloride for osteosarcoma of the femur later developed granulomatous hilar and paratracheal lymphadenopathy and multiple pulmonary nodules. Biopsy of the nodules showed noncaseating granulomas typical of sarcoidosis. Hilar adenopathy and granulomatous pneumonitis have been reported following methotrexate therapy, but a roentgenographic pattern of isolated, discrete pulmonary nodules has not been described. Treatment with immunosuppressive chemotherapy may have inhibited the development of sarcoidosis, which became manifest only after cessation of the chemotherapy.

Cutaneous infection due to mycobacterium szulgai.

A patient on long term corticosteroid therapy for sarcoidosis developed a cutaneous infection due to Mycobacterium szulgai. No evidence of visceral infection with the organism was found during life or at autopsy. The spread of the infection to multiple skin sites probably occurred by autoinoculation.