NSAID treatment with meloxicam enhances peripheral stem cell mobilization in myeloma.

Chemotherapy with G-CSF is used to mobilize peripheral stem cells in multiple myeloma (MM) patients, with plerixafor as a rescue strategy for poorly mobilizing patients. Preclinical studies suggested that the nonsteroidal anti-inflammatory drug meloxicam enhances the mobilization of CD34+ cells. In this single-center study, we evaluated whether adding meloxicam to chemotherapy/G-CSF mobilization increases peripheral hematopoietic CD34+ cell levels and reduces the need of using plerixafor. We prospectively compared two consecutive cohorts of MM patients in first remission mobilized with G-CSF and non-myelosuppressive chemotherapy with vinorelbine or gemcitabine. The second cohort additionally received oral meloxicam. The cohorts comprised 84 patients without meloxicam (-M) and 66 patients with meloxicam (+M). Meloxicam was well tolerated and associated with similar hematologic engraftment after transplantation and equal survival rates. However, the meloxicam group had higher CD34+ cell levels on day 8 of the mobilization procedure (53 200 versus 35 600 CD34+ cells/mL; P=0.007), and fewer patients needed >1 collection day (+M: 6 (9%) patients versus -M: 16 (19%) patients; P=0.04). This resulted in reduced plerixafor administrations (+M: 7 (11%) patients versus -M: 18 (21%) patients; P=0.03) and less costs. Our data suggest that meloxicam enhances the mobilization of hematopoietic CD34+ blood cells in MM patients.

Velocity recovery cycles of human muscle action potentials in chronic renal failure.

OBJECTIVE: To test the hypothesis that muscle fibers are depolarized in patients with chronic renal failure, by measuring velocity recovery cycles of muscle action potentials as indicators of muscle membrane potential. METHODS: Velocity recovery cycles were recorded from brachioradialis muscle by direct muscle stimulation in 13 patients, before, immediately after, and 1h after haemodialysis, and compared with those from 10 age-matched controls. RESULTS: In the patients, supernormality was reduced by 47%, and relative refractory period increased by 60.5% compared with controls (both P<0.001). Dialysis normalized the supernormality, but an hour later it was again reduced. These changes in supernormality were strongly correlated with the changes in serum potassium levels (P<0.0001). A late component of supernormality, attributed to potassium accumulation in the t-tubule system, was also reduced in the patients but remained abnormally low after dialysis. CONCLUSIONS: Muscle membranes in the patients were chronically depolarized by hyperkalemia. Whereas dialysis transiently normalized muscle membrane potential, it was not adequate to normalize t-tubule function. SIGNIFICANCE: Chronic muscle membrane depolarization by hyperkalemia may account for some of the functional deficits in uremic myopathy. Consistent normalization of membrane potential by avoiding hyperkalemia may therefore reduce symptoms of 'uremic myopathy'.

Successful kidney transplantation from donor with Marfan's syndrome.

Marfan's syndrome is caused by mutations in the extracellular matrix protein fibrillin-1 with aortic aneurysm and dissection being its most life-threatening manifestations. Kidney transplantation from donors with Marfan's syndrome has never been reported in the literature, possibly because of reticences due to the underlying connective tissue disease. Here, we report two patients with end-stage renal disease, transplanted with the kidneys from a donor with Marfan's syndrome who died of aortic dissection and cerebral hemorrhage. After delayed graft function in both recipients, renal function normalized with no renovascular complications and negative proteinuria for 6 years in one patient and 2 years in the other patient, who died from an ischemic cerebrovascular insult. Kidneys from organ donors with Marfan's syndrome might be suitable for transplantation.

Oral erythromycin improves gastrointestinal motility and transit after subtotal but not total gastrectomy for cancer.

BACKGROUND: Erythromycin has been shown to be a powerful prokinetic of the gastrointestinal tract. Little is known about its value to improve motility and transit in gastrectomized patients. METHODS: Thirteen disease-free patients subjected to subtotal gastrectomy and 11 subjected to total gastrectomy for gastric cancer entered the study. Gastrointestinal transit of a standard 99mTc-labelled meal and fasting motility were studied before and after oral erythromycin. RESULTS: In patients who had subtotal gastrectomy mean(s.d.) gastric half-emptying time was 42(14) min before and 26(11) min after erythromycin (P = 0.011). Before erythromycin prolonged rhythmical contractions (3 per min) were recorded in eight patients, sporadic non-organized contractions in two and prolonged bursts of waves in one. After erythromycin, clustered waves resembling a migrating motor complex (MMC) appeared in eight patients, while rhythmic motor activity was unchanged in three. In patients who had total gastrectomy jejunal half-emptying time was 39(18) min before and 45(12) min after erythromycin. In eight patients, frequent MMCs were recorded, peristaltic in four, synchronous in one, antiperistaltic in two, with clusters of non-propagated waves in one. After erythromycin, longer peristaltic MMCs were recorded in three, antiperistaltic MMCs persisted in two, synchronous in one and clusters of non-propagated waves in two. CONCLUSION: Oral erythromycin improves gastrointestinal transit and motility after subtotal gastrectomy. The findings after total gastrectomy are controversial.