Alveolar proteinosis (AP) is characterized by excessive surfactant accumulation, and most cases are of unknown etiology. Standard therapy for AP is whole-lung lavage, which may not correct the underlying defect. Because the hematopoietic cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) is required for normal surfactant homeostasis, we evaluated the therapeutic activity of GM-CSF in patients with idiopathic AP. Fourteen patients received 5 microg/kg/d GM-CSF for 6 to 12 wk with serial monitoring of the alveolar-arterial oxygen gradient ([A-a]DO2), diffusing capacity of carbon monoxide, computed tomographic scans, and exercise testing. Patients not responding to 5 microg/kg/d GM-CSF underwent stepwise dose escalation, and responding patients were retreated at disease recurrence. Stored pretreatment sera were assayed for GM-CSF-neutralizing autoantibodies. According to prospective criteria, five of 14 patients responded to 5 microg/kg/d GM- CSF, and one of four patients responded after dose escalation (20 microg/kg/d). The overall response rate was 43% (mean improvement in [A-a]DO2 = 23.2 mm Hg). Responses lasted a median of 39 wk, and were reproducible with retreatment. GM-CSF was well-tolerated, with no late toxicity seen. The only treatment-related factor predictive of response was GM-CSF-induced eosinophilia (p = 0.01). Each of 12 patients tested had GM-CSF-neutralizing autoantibodies present in pretreatment serum. We conclude that GM- CSF has therapeutic activity in idiopathic AP, providing a potential alternative to whole-lung lavage.

The New England Journal of Medicine that both artemether and the closely related compound arteether induce a selective pattern of damage principally to the brain-stem nuclei involved in auditory processing. 3 If the prolongation of coma observed in our study and in the accompanying study from the Gambia was caused by neurotoxicity, then it was reversible. There was no associated neurologic deficit in survivors, and no evidence of auditory abnormalities. The incidence of neurologic sequelae in the Gambian trial was also similar in the two treatment groups. We believe that a definitive statement regarding the relative merits of artemether and quinine should await a systematic overview of many randomized, controlled trials. If this confirms that artemether treatment is associated with a lower mortality rate than quinine, and there is no associated increase in neurologic sequelae, then any effect on the duration of coma will have secondary importance.Dr. Newmark is correct; an error crept into the manuscript. The line should have read, "the correlated QT interval was prolonged to more than 0.5 second." T RAN T INH H IEN

Post-induction aplasia for acute myeloid leukemia/myelodysplastic syndrome is a high-risk period for invasive fungal diseases. The effectiveness of fluconazole, itraconazole solution, voriconazole and posaconazole prophylaxis used consecutively from December 1998 to January 2010 in patients with acute myeloid leukemia/ myelodysplastic syndrome undergoing remission-induction chemotherapy was retrospectively evaluated. A total of 216 consecutive patients received 573 prophylaxis courses. Breakthrough-invasive fungal disease incidence in fluconazole, itraconazole, voriconazole, posaconazole recipients was 25%, 16%, 14% and 3%, respectively. Voriconazole/posconazole versus fluconazole/itraconazole combined was associated with significant reductions in breakthrough-invasive fungal disease incidence (20% vs

In many patients the optimal method of investigation of peripheral pulmonary lesions (PPL) is not clear. We performed a prospective randomized pragmatic trial to determine the comparative effectiveness of endobronchial ultrasound-guided transbronchial lung biopsy (EBUS-TBLB) and CT-guided percutaneous needle biopsy (CT-PNB) for the investigation of PPL. Overall complication rates were higher in those undergoing CT-PNB (27% v 3%, p = 0.03), while diagnostic accuracy of EBUS-TBLB was shown to be non-inferior to that of CT-PNB. Expected diagnostic accuracy and complication rates are likely to differ for individual patients on the basis of specific complex clinicoradiologic factors, which will influence the cost-benefit analysis between EBUS-TBLB and CT-PNB for individual patients. Further studies are required to examine the effect of these factors on clinical decision-making.

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To determine the accuracy of computed tomographic intravenous cholangiography (CT-IVC) for detection of choledocholithiasis. Sixty-five patients undergoing endoscopic retrograde cholangiography (ERC) underwent CT-IVC prior to ERC, using a single detector helical CT following intravenous infusion of 100 ml iotroxate. Patients with bilirubin levels >3 times normal were excluded. ERC was indeterminate in three patients (4.7%) and CT-IVC in four (6.3%). Twenty-three patients had ductal calculi at ERC, and CT-IVC was positive in 22, with two false positives and one false negative: sensitivity 95.6%, specificity 94.3%. Stones were multiple in nine and solitary in 14. Of the 14 solitary stones, ten were

In summary, only 56.6% of ICU patients receiving SAT had CP. Most strains were susceptible to SAT. A similar 28-day mortality rate was observed among groups; the late administration of SAT significantly worsened the prognosis of patients with less severe CP.