rHuEPO dose inversely correlated with the number of circulating CD34+ cells in maintenance hemodialysis patients.

BACKGROUND: A decreased number of endothelial progenitor cells (EPCs) as well as anemia have been reported to be associated with cardiovascular disease. Maintenance hemodialysis (MHD) patients who require higher doses of recombinant human erythropoietin (rHuEPO) have higher cardiovascular mortality. However, it has not been examined whether there is correlation between the numbers of CD34+ cells, including EPCs and erythroid progenitor cells, and the dose of rHuEPO in MHD patients. METHODS: We measured the number of circulating CD34+ cells by flow cytometry and examined the clinical characteristics in 35 MHD patients (50% male). RESULTS: A significant negative correlation was discovered between the number of circulating CD34+ cells and the dose of rHuEPO (r = -0.441, p = 0.013). We performed multivariate regression analysis to determine whether the number of CD34+ cells was associated with age, gender, diabetes, serum albumin, C-reactive protein, ferritin, statin, and dose of rHuEPO. The dose of rHuEPO, diabetes, and statin were independent predictors of the number of circulating CD34+ cells. A reciprocal analysis that divided these patients into two groups according to mean value of CD34+ cells also demonstrated the significant relationship between rHuEPO dose level and the number of CD34+ cells. CONCLUSION: These findings suggested that the requirement of a higher dose of rHuEPO to maintain target hemoglobin was associated with a decrease in the number of CD34+ cells. This relationship may be partly responsible for the higher cardiovascular mortality of this group among MHD patients.

Autologous peripheral blood mononuclear cell implantation for patients with peripheral arterial disease improves limb ischemia.

BACKGROUND: Implantation of bone marrow mononuclear cells, including endothelial progenitor cells, into ischemic limbs has been shown to improve collateral vessel formation. In the present study the safety and feasibility of autologous peripheral blood mononuclear cells (PBMNCs) implantation after granulocyte-colony stimulating factor (G-CSF)-induced mobilization was investigated in patients with severe peripheral arterial disease. METHODS AND RESULTS: Six cases were enrolled: 5 of thromboangitis obliterans and 1 of arteriosclerosis obliterans. Following administration of G-CSF (10 microg . kg(-1) . day(-1)), PBMNCs were harvested and injected intramuscularly (5 legs and 1 arm) for 2 days for the patients with ischemia of the legs. No serious adverse events related to G-CSF administration, harvest or implantation were observed during this study period. Improvement in the ankle - brachial pressure index (ABI: >0.1) was seen in 4 patients at 4 weeks and ischemic ulcers improved in 3 of 3 patients. The mean maximum walking distance significantly increased from 203 m to 559 m (p=0.031) at 4 weeks and was sustained for 24 weeks. Significant improvement was seen in physiological functioning subscale of Short Form-36. CONCLUSION: Implantation of PBMNCs collected after G-CSF administration could be an alternative to therapeutic angioplasty in patients with severe peripheral arterial disease.

Alanine aminotransferase (ALT) levels in a normal population and interferon therapy in chronic hepatitis C patients with normal ALT.

BACKGROUND/AIMS: The aims of this study were to determine the distribution of serum alanine aminotransferase levels in a normal population and to clarify whether interferon treatment is justified in HCV-infected patients with persistently normal alanine aminotransferase levels. METHODOLOGY: The distribution of alanine aminotransferase levels was examined among 949 normal subjects who were negative for hepatitis viruses, denied regular alcohol use. Nineteen patients with chronic hepatitis C and persistently normal alanine aminotransferase levels were treated with alpha interferon (six or ten million units thrice weekly for six months). RESULTS: Peaks of alanine aminotransferase distribution among the normal subjects were seen at 16-20 IU/L and 11-15 IU/L in males and females, respectively. Fourteen of the 19 patients who received interferon treatment had favorable factors of response to interferon (eight with low pretreatment virus load, four with HCV genotype 2 and two with both). A sustained virological response was achieved in eight (57%) of 14, and alanine aminotransferase levels decreased significantly to within the normal range after interferon treatment in six of eight. CONCLUSIONS: Patients with chronic hepatitis C and persistently normal alanine aminotransferase levels should be treated with high doses of interferon if they have favorable factors of response to interferon treatment.