Stimulating the production of fetal hemoglobin may benefit patients with sickle cell anemia by inhibiting sickling. We gave pulsed treatments with high doses of recombinant human erythropoietin to baboons in order to test the hypothesis that the resultant rapid erythroid regeneration would stimulate F cells--i.e., cells that contain fetal hemoglobin. In normal animals, this treatment caused sharp increments in F-reticulocyte levels, which rose from 1 to 2 percent before treatment to 40 to 50 percent afterward. In two animals with chronic anemia and high levels of endogenous erythropoietin, recombinant human erythropoietin induced further increments in F-reticulocyte levels, which rose in one animal from 6 to 8 percent before treatment to 23 percent after treatment, and in the other from 20 percent before to 50 percent afterward. The time course of F-reticulocyte stimulation suggested that these cells were the products of mobilized early erythroid progenitors. These results raise the possibility that pulses of erythropoietin could be used to stimulate F-cell formation in patients with sickle cell disease.

Nocardiosis is a cause of significant morbidity and mortality in the immunocompromised host, and is an infrequent complication of tumor necrosis factor alpha (TNF-alpha) blockers in chronic inflammatory diseases. Nocardiosis occurs at a rate of 3.55 and 0.88 per 100 000 patients treated with infliximab or etanercept, respectively. Disseminated nocardiosis remains an uncommon complication of these agents. Here, we present a fatal case of disseminated systemic nocardiosis in a patient with psoriasis following sequential therapy with alefacept and then infliximab therapy. The patient developed disseminated disease involving the brain, lymph nodes, and adrenal glands. The diagnosis was made by blood culture and aspiration of the adrenal gland abscess, which revealed Gram-positive bacilli and later grew Nocardia farcinica. The organism was identified by DNA sequencing, and was susceptible to moxifloxacin, gatifloxacin, ciprofloxacin, amoxicillin-clavulanic acid, linezolid, sulfamethoxazole, and amikacin. It was resistant to clarithromycin, ceftriaxone, and tobramycin and was intermediately susceptible to imipenem.

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Chronically anemic baboons on a continuous hydroxyurea regimen were treated with pulsed doses of recombinant human erythropoietin (rHuEpo) to test whether the combination of these two compounds, which individually induce F-cell production, can enhance further F-cell output. A low-F-cell-responding animal under chronic hydroxyurea treatment was given three separate pulses of Epo and responded with F- reticulocyte increments that were similar to the sum increments caused by either hydroxyurea alone or rHuEpo alone. The same results were obtained in a high-F-responding animal similarly treated. These findings suggest that rHuEpo and hydroxyurea can increase F cell numbers in an additive fashion. It is speculated that both compounds act through perturbation of erythroid differentiation kinetics.