Fever, petechiae, and pulmonary infiltrates in an immunocompromised Peruvian man.

The diagnostic considerations raised by immunocompromised patients with opportunistic infection continue to expand. When such patients harbor latent or persistent infection acquired in a tropical environment, the diagnostic challenge is even greater. The Infectious Disease Service at Yale-New Haven Hospital was asked to see a middle-aged man from Peru with known T-cell lymphoma who had recently completed a course of chemotherapy. He presented to the hospital with fever, petechial skin rash, pulmonary infiltrates, and neutropenia. Ultimately this case illustrated the necessity for careful evaluation of such patients, looking, in particular, for evidence of opportunistic parasitic infection.

Sulfasalazine-induced pulmonary disease.

Sulfasalazine has been widely used in the treatment of inflammatory bowel disease. Although a high incidence of side effects has been reported, pulmonary complications are rare. The clinical, radiographic, and histological abnormalities that occurred in a patient three months after initiation of sulfasalazine are described. A review of the literature suggests that the possibility of drug-induced pulmonary disease should be considered in any patient with inflammatory bowel disease receiving treatment with sulfasalazine who develops symptoms or radiographic evidence of pulmonary disease. Transbronchial biopsy may be useful in confirming the type of pulmonary injury.

Pulmonary endothelial dysfunction in the presence or absence of interstitial injury induced by intratracheally injected bleomycin in rabbits.

Previously, we reported that repeated subcutaneous administration of bleomycin (BLM) to rabbits produced functional and structural endothelial damage with no evidence of interstitial fibrosis. In the present study, rabbits received intratracheally a single injection of BLM (6 units/kg, n = 6: "low dose" or 11 units/kg, n = 4: "high dose"); 6 additional animals received intratracheally an injection of saline and served as controls. Four weeks after BLM administration, the low-dose group demonstrated significant reduction in the single-pass pulmonary removal of 14C-5-hydroxytryptamine (5-HT) (p less than 0.05; n = 4), whereas 3H-norepinephrine (NE) removal and 3H-benzoyl-phe-ala-pro (BPAP) substrate for lung angiotensin converting enzyme (ACE) metabolism in vivo, as well as lung and serum ACE activity in vitro remained at control levels. No morphologic or biochemical evidence of fibrosis was observed. In contrast, the high-dose BLM group exhibited significant reductions in 14C-5-HT and 3H-NE removal and 3H-BPAP metabolism in vivo, but no significant changes in lung or serum ACE activity in vitro. Furthermore, there was evidence of fibrosis, as revealed by a 59% increase in lung hydroxyproline content and by light microscopic examination of lung tissue. We conclude that intratracheal administration of BLM to rabbits can produce endothelial dysfunction in the presence or absence of interstitial injury.

Prolonged reduction in serum angiotensin converting enzyme activity after treatment of rabbits with bleomycin.

Previous work from this laboratory (J. S. Lazo, J. D. Catravas, and C. N. Gillis, Biochem. Pharmacol. 30, 2577-2584, 1981; J. D. Catraveras, J. S. Lazo, and C. N. Gillis, J. Pharmacol. Exp. Ther. 217, 524-529, 1981) demonstrated that subacute bleomycin (BLM) administration (5 mg/kg) to rabbits three times weekly for 4 weeks produced a marked decrease in serum angiotensin converting enzyme (ACE) activity in addition to producing both morphological and biochemical evidence of pulmonary endothelial damage. In this work, the reversibility of the decreased serum ACE activity and the biochemical and morphological status of the pulmonary endothelium after a substantial drug-free period in rabbits was examined. Rabbits were injected sc three times weekly for 4 weeks with vehicle or BLM (5 mg/kg) and then maintained drug free for an additional 6 or 7 weeks. Serum ACE activity decreased over 60% during the BLM treatment but did not return to control levels at any time during the drug-free period. The pulmonary endothelium, however, appeared undamaged. No decrease in pulmonary ACE activity was detected either in vitro or in vivo nor was the single-pass pulmonary removal in vivo of [3H]norepinephrine and 5-[14C]hydroxytryptamine different between BLM-treated and control rabbits after the drug-free period. In addition, no evidence of pulmonary endothelial damage was observed by light and electron microscopy. Thus, reduction in serum ACE activity appears to be a durable reflection of BLM toxicity in rabbits that persists even in the absence of any detectable biochemical or morphologic endothelial injury.

Clinical and immunologic response to antigen-specific transfer factor in drug-resistant infection with Mycobacterium xenopi.

The administration of transfer factor obtained from three donors who had recovered from clinical infections with Mycobacterium xenopi to a patient who had a destructive pulmonary infection with this organism, was associated with the reversal of an unfavorable clinical course. Cavitary tuberculosis associated with resistance to all combinations of antituberculosis drugs was probably related to a concurrent depression of cell-mediated immunity of unknown origin. Antigen specific but not nonspecific transfer factor caused a rapid and prolonged improvement in both the pulmonary disease and the immunologic deficiency. Cross-reactivity between the antigenic determinants of M. xenopi and Mycobacterium tuberculosis made it possible to use transfer factor obtained from donors responsive to purified protein derivative of tuberculin. This study clearly demonstrates the additional benefits to be gained from using transfer factor that is antigen-specific in the treatment of infectious diseases.

Early detection of oxygen-induced lung injury in conscious rabbits. Reduced in vivo activity of angiotensin converting enzyme and removal of 5-hydroxytryptamine.

Changes in lung endothelial metabolic function, determined in vitro, have been proposed as sensitive indexes of hyperoxic lung damage. However, it is unclear whether these changes are also seen in vivo. We studied the possibility, using conscious rabbits in which jugular and carotid catheters had previously been placed under halothane anesthesia. Approximately 24 h later, test animals were exposed to normobaric hyperoxia (96 +/- 2%), while a second group was maintained in room air. Multiple indicator dilution methods were used to study (1) metabolism of 3H-benzoyl-phe-ala-pro (BPAP), a synthetic substrate for angiotensin converting enzyme (ACE), and (2) removal of 14C-5-hydroxytryptamine (5-HT) during a single transpulmonary passage in conscious animals. Determinations were made serially during exposure (room air or hyperoxia) or until death occurred in the oxygen-treated animals. Lungs of air-exposed animals hydrolyzed 81 +/- 2% of injected BPAP (0.1 to 0.15 nmoles) during a single passage. Percent metabolism was unaltered during the next 72 h. However, in test animals, ACE activity, as reflected by BPAP metabolism, was significantly reduced after 16 h of exposure to oxygen (77 +/- 2%, p less than 0.01) and continued to decrease to a nadir of 66 +/- 3% at 40 h. Single-pass lung uptake of 14C-5-HT (77 +/- 2%) was unchanged throughout the 72-h period in air-exposed rabbits. In test animals, 14C-5-HT removal decreased to 65 +/- 4% (p less than 0.01) after 24 h of oxygen exposure; 5-HT removal remained depressed compared with the 0 h control determination for the oxygen group at all subsequent measurement intervals. Light and electron microscopy of lungs from oxygen-exposed rabbits demonstrating reduced 5-HT removal and ACE activity at 24 h revealed normal endothelial and type I cell morphologic features. We conclude that exposure to 100% oxygen produced significant reduction in pulmonary 5-HT removal and BPAP metabolism prior to the onset of morphologic damage.