Induction and maintenance therapy with intermittent interleukin-2 in HIV-1 infection

Studies establishing that intermittent subcutaneous interleukin-2 (IL-2) therapy can lead to substantial CD4 cell increases in many HIV-infected patients have generally been of limited duration. We studied 77 patients participating in active longitudinal studies of subcutaneous IL-2 therapy at our center in order to determine the long-term feasibility of this approach. Following initial induction, patients in each trial were eligible to receive intermittent 5-day cycles of subcutaneous IL-2 treatment at individualized doses and frequencies capable of maintaining CD4 counts at postinduction levels. The mean duration of study participation to date is 5.9 years (range, 1.0-9.3 years). Mean baseline CD4 cell count and CD4 percent values of 0.521 x 10(9)/L (521 cells/microL) and 27% have risen to 1.005 x 10(9)/L (1005 cells/microL) and 38%, respectively, at 90 months. The mean number of subcutaneous IL-2 cycles required to achieve and maintain these increases was 10 cycles (range, 3-29 cycles), and the current mean interval of cycling required to maintain these elevations is 39 months (median, 35 months; range, 2-91 months). We conclude that subcutaneous IL-2 therapy is capable of maintaining CD4 cell increases for an extended period using a remarkably low frequency of intermittent cycling. These observations may contribute to patients' acceptance of subcutaneous IL-2 as a favorable long-term treatment strategy.     

Phase 1/2 study of the combination of 5-aza-2'-deoxycytidine with valproic acid in patients with leukemia

We conducted a phase 1/2 study of the combination of 5-aza-2'-deoxycytidine (decitabine) and the histone deacetylase inhibitor valproic acid (VPA) in patients with advanced leukemia, including older untreated patients. A group of 54 patients were treated with a fixed dose of decitabine (15 mg/m(2) by IV daily for 10 days) administered concomitantly with escalating doses of VPA orally for 10 days. A 50 mg/kg daily dose of VPA was found to be safe. Twelve (22%) patients had objective response, including 10 (19%) complete remissions (CRs), and 2 (3%) CRs with incomplete platelet recovery (CRp). Among 10 elderly patients with acute myelogenous leukemia or myelodysplastic syndrome, 5 (50%) had a response (4CRs, 1CRp's). Induction mortality was observed in 1 (2%) patient. Major cytogenetic response was documented in 6 of 8 responders. Remission duration was 7.2 months (range, 1.3-12.6+ months). Overall survival was 15.3 months (range, 4.6-20.2+ months) in responders. Transient DNA hypomethylation and global histone H3 and H4 acetylation were induced, and were associated with p15 reactivation. Patients with lower pretreatment levels of p15 methylation had a significantly higher response rate. In summary, this combination of epigenetic therapy in leukemia was safe and active, and was associated with transient reversal of aberrant epigenetic marks.     

Eosinophilic angiocentric fibrosis of the sinonasal tract: report on the clinicopathologic features of a case and review of the literature

BACKGROUND: Eosinophilic angiocentric fibrosis (EAF) is a rare fibroinflammatory lesion of the sinonasal tract that occurs mainly in young to middle-aged female patients. Only two previous cases affecting male patients have been reported, and its etiopathogenesis remains unknown. The authors report on the third case of the entity in a male patient and review the 12 previously reported cases. CASE REPORT: A 52-year-old male patient was initially seen with a 15 years history of allergic rhinitis, progressive nasal obstruction, and left-sided hearing loss. All laboratory tests were unremarkable, except the nasal discharge eosinophil count that showed a conspicuous eosinophilia. The video-assisted-nasofibroscopic examination and CT scans disclosed a thickened deviated nasal septum with a subjacent infiltrative lesion. The histologic analysis of the nasal septum showed a variable mixed inflammatory cellular infiltration mainly composed of eosinophils, plasma cells, and histiocytes with a perivascular distribution; in other areas, an angiocentric fibrosing lesion with a peculiar perivascular onion-skin pattern was observed. The patient had a partial resection of the lesion with symptomatic control. CONCLUSIONS: The presence of rhinitis and nasal eosinophilia in our case associated with the clinical aspects of the previously reported cases further support an allergic cause for EAF.     

Nonanatomic Thoracoscopic Wedge Resection for Diffuse Lung Disease and Indeterminate Pulmonary Nodule

Video technology has revolutionized thoracoscopy dramatically, considerably increasing its indications. The clinical charts of patients who underwent a video-thoracoscopic procedure during a 6-year period were reviewed. Any patient in whom lung wedge resection for diffuse disease or an indeterminate nodule was performed met the inclusion criteria. Early and long-term outcomes were analyzed. A total of 310 thoracoscopic procedures were performed in the 250 patients reviewed. Of these patients, 60 presented with diffuse lung disease and 71 with an indeterminate pulmonary nodule. The total morbidity among diffuse disease patients was 5% (one intercostal vessel hemorrhage and two air leaks). Overall mortality for this group was 11% and was related to previous respiratory status and underlying disease. Patients not requiring preoperative mechanical ventilation ended up requiring it postoperatively, for a crossover rate of 23%. There was no morbidity or mortality in patients who did not require mechanical ventilation. The therapeutic impact index (defined as the total number of patients divided by the patients in whom initiation or withdrawal of specific treatment was due to the biopsy result) for diffuse lung disease was 0.9. Regarding lung nodule resection, early morbidity was present in one patient, who developed a persistent air leak. Late morbidity was present in three patients, who developed persistent intercostal pain. Total morbidity was 5.6%. No mortality was observed for this group. Nonanatomic wedge resection via video-thoracoscopy for diffuse pulmonary disease and indeterminate lung nodule is feasible using minimally invasive methods. Morbidity and mortality are related to the underlying disease and the respiratory status; they are not necessarily due to the procedure.     

Comparison of the photodynamic fungicidal efficacy of methylene blue, toluidine blue, malachite green and low-power laser irradiation alone against Candida albicans

This study was to evaluate specific effects of photodynamic therapy (energy density 15.8 J/cm², 26.3 J/cm² and 39.5 J/cm²) using methylene blue, toluidine blue and malachite green as photosensitizers and low-power laser irradiation on the viability of Candida albicans. Suspensions of C. albicans containing 10⁶ cells/ml were standardized in a spectrophotometer. For each dye, 120 assays, divided into four groups according to the following experimental conditions, were carried out: laser irradiation in the presence of the photosensitizer; laser irradiation only; treatment with the photosensitizer only; no exposure to laser light or photosensitizer. Next, serial dilutions were prepared and seeded onto Sabouraud dextrose agar for the determination of the number of colony-forming units per milliliter (CFU/ml). The results were subjected to analysis of variance and the Tukey test (P < 0.05). Photodynamic therapy using the photosensitizers tested was effective in reducing the number of C. albicans.. The number of CFU/ml was reduced by between 0.54 log₁₀ and 3.07 log₁₀ and depended on the laser energy density used. Toluidine blue, methylene blue and malachite green were effective photosensitizers in antimicrobial photodynamic therapy against C. albicans, as was low-power laser irradiation alone.