Establishing a cord blood banking and transplantation program in Mexico: a single institution experience.

BACKGROUND: Over the past decade, umbilical cord blood (UCB) banking and transplantation have increased significantly worldwide. The experience in developing countries, however, is still limited. In January 2005 the Mexican Institute of Social Security (IMSS) initiated its UCB banking and transplantation program. This study reports on the experience generated at this institution during the first 2 years of activities. STUDY DESIGN AND METHODS: A public UCB bank was established at La Raza Medical Center, IMSS, in Mexico City. Good manufacturing practices and standard operating procedures were used to address donor selection, as well as UCB collection, processing, and cryopreservation. Based mainly on human leukocyte antigen (HLA) and total nucleated cell (TNC) content, specific UCB units were thawed, processed, and released for transplantation. RESULTS: Based on stringent selection criteria, 360 UCB units were collected from January 2005 to December 2006. A total of 201 (56%) units (minimum volume, 50 mL without anticoagulant) were processed and stored. Median values for specific parameters were as follows: volume, 89.9 mL; viability, 94.8%; TNCs, 0.91 x 10(9); CD34+ cells, 3.13 x 10(6); and colony-forming cells, 1.20 x 10(6). During this period, 10 units had been released for transplantation to seven patients (six children and one adult). Engraftment was observed in five patients; four of them were still in remission (114-293 days after transplant). In spite of showing sustained engraftment, one patient died on Day +88. Two patients showed no engraftment and died 29 to 30 days after transplant. CONCLUSION: The results obtained during this initial period are encouraging and indicate that the UCB banking and transplantation program at IMSS will help to improve already existing hematopoietic cell transplant programs in Mexico. The experience generated at IMSS may be helpful to other institutions, particularly those in developing countries.

Prevention of irinotecan associated diarrhea by intestinal alkalization. A pilot study in gastrointestinal cancer patients.

AIM AND BACKGROUND: Intestinal alkalization could prevent irinotecan associated diarrhea modulating some chemical equilibria between irinotecan metabolites. The aim of this study was to evaluate the efficacy of this procedure in advanced gastrointestinal cancer patients (GICP). MATERIALS AND METHOD: In this prospective study advanced GICP, receiving irinotecan based chemotherapy regimens, were well trained to add sodium bicarbonate to the water intake in order to accomplish intestinal alkalization. RESULTS: A total of twenty four advanced GICP were enrolled. Grade III-IV diarrhea has been observed in four patients (16%), some of whom had several risk factors for diarrhea. Only one out of seventeen colorectal cancer patients, receiving the irinotecan combination as first line therapy, had grade III-IV diarrhea. No side effects of the procedure have been appreciated. CONCLUSIONS: Intestinal alkalization may be effective as a preventive treatment for irinotecan associated diarrhea in chemotherapy regimens used in GICP. This procedure deserves further investigation.

C-reactive protein induces matrix metalloproteinase-1 and -10 in human endothelial cells: implications for clinical and subclinical atherosclerosis.

OBJECTIVES: We examined the effect of C-reactive protein (CRP) on matrix metalloproteinase (MMP) and inhibitor expression in endothelial cells and in patients with clinical and subclinical atherosclerosis. BACKGROUND: In addition to predicting atherosclerotic vascular disease, CRP may directly promote a proinflammatory/proatherosclerotic phenotype. METHODS: Human umbilical vein endothelial cells (HUVECs) and aortic endothelial cells (HAECs) were incubated in the presence or absence of CRP (50 mug/ml). Microarray analysis, real-time polymerase chain reaction, immunological and activity assays for MMPs were performed. Specific inhibitors of mitogen-activated protein kinase pathway were used. The MMP-1 and -10 plasma levels were measured in apparently healthy subjects (n = 70). Immunolocalization of CRP, MMP-1, and MMP-10 was performed in human mammary arteries and carotid endarterectomy specimens. RESULTS: C-reactive protein augmented MMP-1 and -10 messenger ribonucleic acid expression in HUVEC (p < 0.05) and HAEC (p < 0.01). C-reactive protein stimulation also increased MMP-1 and -10 protein in conditioned culture medium (p < 0.001), as well as MMP activity (p = 0.001). Specific inhibition of p38 or MEK abolished the CRP induction of the MMP-1, whereas MMP-10 induction blockade required the simultaneous inhibition of p38 and Jun N-terminal kinase pathways. Subjects with CRP values >3 mg/l (n = 37) had increased plasma MMP-1 and -10 (p < 0.05), the association being significant after adjustment for confounding variables (p = 0.04 and p = 0.008, respectively). The MMP-10 levels were elevated in subjects with higher carotid intima-media thickness (p = 0.009). Increased CRP and MMP-10 colocalized in endothelial layer and macrophage-rich areas in advanced atherosclerotic plaques. CONCLUSIONS: Increased local and systemic CRP-related MMP activation might provide a link between inflammation and plaque vulnerability.

Prevention of irinotecan associated diarrhea by intestinal alkalization. A pilot study in gastrointestinal cancer patients

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Aim and background. Intestinal alkalization couldprevent irinotecan associated diarrhea modulatingsome chemical equilibria between irinotecan metabolites.The aim of this study was to evaluate the efficacyof this procedure in advanced gastrointestinalcancer patients (GICP).Materials and method. In this prospective studyadvanced GICP, receiving irinotecan based chemotherapyregimens, were well trained to add sodiumbicarbonate to the water intake in order to accomplishintestinal alkalization.Results. A total of twenty four advanced GICP wereenrolled. Grade III-IV diarrhea has been observedin four patients (16%), some of whom had severalrisk factors for diarrhea. Only one out of seventeencolorectal cancer patients, receiving the irinotecancombination as first line therapy, had grade III-IVdiarrhea. No side effects of the procedure have beenappreciated.Conclusions. Intestinal alkalization may be effectiveas a preventive treatment for irinotecan associateddiarrhea in chemotherapy regimens used in GICP.This procedure deserves further investigation

The decrease in plasma ghrelin concentrations following bariatric surgery depends on the functional integrity of the fundus.

BACKGROUND: Gastric bypass surgery, which involves the production of a reduced stomach pouch,has been shown to markedly suppress circulating ghrelin concentrations. Since bypassing the ghrelin-producing cell population may be relevant to the disruption of fundic-derived factors participating in food intake signaling, the effect of weight loss induced by either adjustable gastric banding (AGB), Roux-en-Y gastric bypass (RYGBP) or biliopancreatic diversion (BPD) was studied. METHODS: 16 matched obese patients [35.0 + 2.4 years; initial body weight 124.8 +/- 5.7 kg; body mass index (BMI) 47.1 +/- 2.2 kg/m(2)] in whom similar weight loss had been achieved by either AGB (n=7), RYGBP (n=6) or BPD (n=3) were studied. Blood was obtained for biochemical and hormonal analyses. Body composition was assessed by air-displacement-plethysmography. RESULTS: Comparable weight loss (AGB: 26.1 +/- 5.1 kg; RYGBP: 32.1 +/- 5.0; BPD: 31.7 +/- 6.1; P=NS) and decrease in percentage body fat (AGB: 10.0 +/- 1.5%; RYGBP: 14.2 +/- 2.8; BPD: 10.3 +/- 1.0; P=NS) induced by bariatric surgery exerted significantly different (P=0.004) effects on plasma ghrelin concentrations, depending on the surgical procedure applied (AGB: 480 +/- 78 pg/ml; RYGBP: 117 +/- 34; BPD: 406 +/- 86). Without significant differences in BMI, body fat, glucose, triglycerides, cholesterol, insulin and leptin levels, patients who had undergone the RYGBP exhibited statistically significant diminished circulating fasting plasma ghrelin concentrations compared with the other two bariatric techniques which conserve direct contact of the fundus with ingested food (P=0.003 vs AGB and P=0.020 vs BPD). CONCLUSION: Fasting circulating ghrelin concentrations in patients undergoing diverse bariatric operations depend on the degree of dysfunctionality of the fundus.