Murine leukemia inhibitory factor enhances retroviral-vector infection efficiency of hematopoietic progenitors

We have investigated the in vitro effects of the cytokine leukemia inhibitory factor (LIF) on normal murine hematopoietic progenitors by measuring recovery and retroviral vector infection efficiency of 13-day posttransplant, spleen-colony-forming cell (CFU-S 13) in short-term culture. Up to a twofold increase in CFU-S13 recovery was observed, from 9.7 x 10(-5) cells in untreated controls to 17.8 to 19.5 x 10(-5) cells, depending on the concentration of LIF. Histologic analysis of spleen colonies from control and LIF-treated marrows demonstrated that there was no detectable alteration in the differentiative potential of CFU-S13. The efficiency of CFU-S13 infection was increased from 15% in untreated controls to 84% to 91% in LIF-treated marrows. Analysis of proviral integration sites in spleen colonies indicated that some CFU- S13 precursors were infected in the LIF-treated marrows.     

Monitoring of kidney function in HIV‐positive patients

HIV‐positive patients are at increased risk of developing chronic kidney disease. Although guidelines recommend regular monitoring of renal function in individuals living with HIV, the optimal frequency remains to be defined. In this review, we discuss the renal syndromes that may be identified at an earlier stage via routine assessment of kidney function, and provide guidance in terms of the frequency of monitoring, the most useful tests to perform, and their clinical significance. Specifically, we address whether annual monitoring of kidney function is appropriate for the majority of HIV‐positive patients.     

Breast cancer patients have increased risk of developing mTOR inhibitor‐associated stomatitis

A total of 115 patients who used everolimus were evaluated. The mean age was 57 (±13.3) years old, and 87 patients were women (75.6%). mTOR inhibitor‐associated stomatitis (mIAS) was observed in 36 patients (31.3%). The lesions ranged from 0.5 cm to 1.5 cm, and the tongue was the main site affected. In addition, 21 patients (58.3%) required a dose reduction of everolimus due to mIAS. Patients who had breast cancer presented 2.29‐fold higher risk for developing mIAS when compared to patients with kidney or neuroendocrine tumors. This study emphasizes the high prevalence of mIAS in patients using everolimus, in particular, in patients with breast cancer.     

Magnetic resonance imaging-detected avascular osteonecrosis in systemic lupus erythematosus: lack of correlation with antiphospholipid antibodies

We determined prospectively the prevalence of avascular osteonecrosis (AON) by magnetic resonance imaging (MRI) of both lower limbs in a group of 40 systemic lupus erythematosus (SLE) patients, and correlated the results with their serum antiphospholipid antibody (APL Ab) status and their glucocorticoid (GC) intake. APL Ab were detected by anticardiolipin ELISA and by lupus anticoagulant assays. Cumulated prednisolone doses were computed by chart review. The prevalence of AON was 37.5%, with most patients being asymptomatic despite involvement of multiple sites. The number of epiphyseal, metaphyseal and diaphyseal AON sites per patient did not differ between APL Ab-positive and APL Ab- negative patients nor between patients with high and low APL Ab titres. By contrast, a striking correlation was found between the prevalence and severity of AON and GC therapy. In conclusion, this prospective MRI study indicates that the prevalence of AON in SLE patients correlates strongly with GC therapy, but not with APL Ab status.      

Syndrome of recurrent increased secretion of antidiuretic hormone following multiple doses of vincristine

The syndrome of inappropriate antidiuretic hormone secretion (SIADH) has been recognized to occur following treatment with vincristine. None of the reports have provided information regarding its potential for recurrence on further challenge with vincristine (VCR), an agent generally required for repeated use in patients with malignancies. Symptomatic hyponatremia and SIADH that occurred 8 days following administration of VCR in a child with acute lymphatic leukemia was documented with specific radioimmunoassay of urinary ADH levels. The further occurrence of recurrent elevations in ADH excretion 8-10 days following repeated treatment with VCR was also observed. However, SIADH was prevented by prophylactic rigorous fluid restriction. The occurrence of SIADH following VCR therefore does not preclude the further safe usage of this drug.     

Tissue-factor coagulant activity of cultured human endothelial and smooth muscle cells and fibroblasts

The tissue-factor (thromboplastic) activity of cultured human endothelial cells and fibroblasts is low at time of transfer into fresh medium but increases 3-10 fold. Endothelial cells reach peak activity (400 U/10(5) cells) 5-8 hr after subculture. Activity in fibroblast cultures peaks (3000-12,000 U/10(5) cells) 7-12 hr after subculture. After attaining maximum activity, endothelial and fibroblast tissue- factor content decreases in a time course similar to other cells studied in this laboratory, approaching basal levels by 24-50 hr after subculture. If medium over fibroblasts is changed every 12 hr, activity can be sustained at the peak level for an additional day but cannot be maintained at a high level indefinitely. The kinetics of expression of smooth muscle cell tissue factor are markedly different from other cell types. There is always a pronounced lag (30 hr or more) before the activity increases, and then, in most cases, there is no subsequent decline in activity even though the cells are not refed or restimulated. The activity of each of these cell types is cryptic but becomes available after freeze-thaw disruption of cells.