Inorganic arsenic content in Ecuadorian rice-based products.

Arsenic intake in the world is linked with drinking water and food; the main sources of inorganic As (i-As) exposure in food are rice and rice-based products. The consumption of rice in Ecuador is 53.2 kg year-1 and it is the most commonly used cereal for the preparation of many popular dishes especially for subjects with celiac disease. Objectives of this research were: (i) to determine the content of i-As in foods widely consumed by Ecuadorians with celiac disease, (ii) to calculate the i-As dietary intake, and (iii) to model and predict the health risks of the population under study as a result of their exposure to i-As from rice-based food. The estimated daily intakes of Ecuadorian children (below 3 years of age) and adults were established at 0.52 and 0.55 µg kg-1 body weight d-1, respectively. These values were above the lower BMDL01 value established for i-As established by the EFSA; consequently, it can be concluded that health risk cannot be excluded for the Ecuadorian population with celiac disease.

Immobilization of lipases in hydrophobic chitosan for selective hydrolysis of fish oil: The impact of support functionalization on lipase activity, selectivity and stability.

The objective of this paper was to carry out an integral study of the use of hydrophobic chitosan as a low-cost support for immobilizing lipases and their further application in the selective hydrolysis of fish oil. Chitosan functionalized with different alkyl chains (C4, C8, C12) were characterized by FTIR, TGA, SEM, and Rose Bengal adsorption. Lipase B from Candida antarctica (CalB) and lipase from Rhizomucor miehei (RML) were immobilized obtaining a higher expressed activity at a longer alkyl chain length of support. Biocatalyst thermal stability showed that the impact of the alkyl chain length on enzyme stabilization varied according to the lipase source. The biocatalysts were applied in menhaden oil hydrolysis. Total polyunsaturated fatty acids released after 30 h of reaction with lipases immobilized in butyl, octyl and dodecyl-chitosan was 60, 107, and 90 mM for CalB biocatalysts, and 560, 392, and 50 mM for RML biocatalysts, respectively. Selectivity of CalB was not affected by the alkyl chain, while in the case of RML, a higher selectivity to cis-4,7,10,13,16,19-docohexaenoic acid release was obtained with dodecyl-chitosan. In conclusion, the adequate functionalization of chitosan varied according to lipase source, affecting their activity, stability and performance in the hydrolysis of fish oil.

[Usefulness of intracoronary therapy with progenitor cells in patients with dilated cardiomyopathy: Bridge or alternative to heart transplantation?]. / Utilidad de la terapia intracoronaria con células progenitoras en pacientes con miocardiopatía dilatada: ¿puente o alternativa al trasplante cardiaco?

INTRODUCTION AND OBJECTIVES: Some paediatric publications have recently raised the value of intracoronary therapy with autologous bone marrow-derived progenitor cells (APCs) in children with dilated cardiomyopathy (DCM) and heart failure. We describe the usefulness of this treatment in two infants with severe DCM and heart failure, who had been transferred to our hospital for cardiac transplant evaluation. PATIENTS AND METHODS: The first patient was a 3 months old male weighing 4 kg. The second was a 4 months old male weighing 5 kg. At the time of admission, both were in poor clinical condition (NYHA IV), with severe dilation and systolic dysfunction (ejection fraction [EF]<30%) of the left ventricle and marked elevation of NT-proBNP, requiring treatment with mechanical ventilation and inotropic iv infusion. After mobilization with G-CSF for 4 days, APCs were obtained from peripheral blood by leukocytapheresis, administering them by a slow intracoronary bolus injection using a stop-flow technique (6.15x106 CD34-positive cells/Kg in the first patient, and 10.55x106 CD34-positive cells/Kg in the second). RESULTS: Since the first week after the procedure, clinical status of patients improved and echocardiography showed a decrease in left ventricular dilation. A month later, there was a significant improvement in EF (> 40%) and NT-proBNP levels, subsequently maintained throughout the follow-up. However, four months later in the first patient, the left ventricle dilated again and its function slightly worsened, but without any significant impact in his clinical status. CONCLUSIONS: Intracoronary therapy with APCs can be an alternative in children, especially infants, with DCM and heart failure. It can reduce the waiting list mortality, improve clinical status and provide more time on the waiting list to receive a suitable organ, or even to make transplantation unnecessary.

The occurrence of adverse events during the infusion of autologous peripheral blood stem cells is related to the number of granulocytes in the leukapheresis product.

Toxicity related to autologous PBSC infusion is well known and traditionally attributed to the presence of DMSO as cryoprotectant. But despite DMSO depletion, adverse events continue appearing. We have conducted a retrospective study to determine the incidence of adverse events related to the PBSC infusion in a large series of 144 patients. Adverse effects were observed in 67.36% of patients, although most of them were of grade 1 or 2. The adverse events most frequently reported were allergic reactions, followed by general, gastrointestinal and respiratory symptoms. In the univariate analysis, age (P=0.01), the volume infused (P=0.005), the amount of DMSO (P=0.008), the total nucleated cells (P=0.002), the total number of granulocytes (P=0.000001) and clumping (P=0.000001) were associated with the occurrence of adverse events. In the multivariate analysis, two protective factors, age (P=0.05) and sex (P=0.004), and two risk factors, the number of granulocytes, with a relative risk of 1.18 (95% confidence interval, 1.06-1.31) (P=0.002), and clumping, with an relative risk of 1.94 (95% confidence interval, 1.15-3.29) (P=0.013), were identified. The best cutoff point for the prediction of the occurrence of adverse events, with a sensitivity of 47% and specificity of 89%, was 6.065 x 10(9) granulocytes.

Analysis of factors affecting PBPC collection in low-weight children with malignant disorders.

BACKGROUND: PBPC collection in children weighing

[Cases of neurological symptoms associated with star anise consumption used as a carminative]. / Casos de enfermedad de sintomatología neurológica asociados al consumo de anís estrellado empleado como carminativo.

BACKGROUND: Since March 2000, a series of infants with serious gastrointestinal and neurological symptoms have been observed in Spain. These symptoms were suspected to be associated with the use of star anise infusion. We performed an epidemiological study to determine the characteristics of these patients and to evaluate the association between the symptoms and anise consumption. METHOD: From February to September 2001, a matched case-control study (1:2) was performed among infants aged less than 3 months admitted to the pediatric emergency departments of two hospitals in Madrid. Mantel-Haenszel and conditional logistic regression odds ratios (OR) were calculated to quantify the association and the dose-response relationship. Laboratory analyses of the implicated substances were performed. RESULTS: Twenty-three cases were studied. The mean age was 29.2 days (SD: 25.5). The symptoms observed were irritability, abnormal movements, vomiting and nystagmus. Eighteen cases and 36 controls were included in the case-control study. Nine controls (25 %) consumed anis infusion (consumption was high in five and low in four). The Mantel-Haenszel OR was 18.0 (2.03-631) and the OR for the dose-response relationship was 11.7 (95 % CI: 1.3-188.5) for low levels of consumption and 18.2 (95 % CI: 1.8-183.5) for high levels. Laboratory analyses revealed contamination of Illicium verum by Illicium anisatum. CONCLUSIONS: This study confirms the association between the symptoms described and the use of anise infusion. The dose response analyses provide further evidence for the association. Cross-contamination was found between the product and other anise species. We recommend destruction of the contaminated products, avoidance of anise infusions among infants, and dissemination of the results among pediatricians.

Secondary acute myeloid leukemia and myelodysplasia after autologous peripheral blood progenitor cell transplantation.

Secondary myelodysplastic syndrome (MDS) and acute leukemia (AL) are well-known complications of antineoplastic therapy. The incidence of these serious complications after autologous hematopoietic transplantation ranges from 1.1% to 24%. Prior chemotherapy is its most likely cause, but other variables related to these long-term complications are seriously discussed. There is evidence that priming of progenitor cells isolated from peripheral blood with chemotherapy is also related to a higher risk of secondary MDS/AL. Whether progenitor cells isolated from bone marrow or peripheral blood after mobilization only with cytokines are related to higher risk is a controversial issue. In this paper, we analyze the incidence and variables related to these complications in a series of 99 patients diagnosed with lymphoma or multiple myeloma who underwent autologous transplantation using hematopoietic progenitors isolated from peripheral blood mobilized with granulocyte colony-stimulating factor (G-CSF). The probability of MDS/AL in patients alive 5 years after transplant in our series is 8.58%, similar to that reported in other series using bone marrow grafts. The total dose of cyclophosphamide ( p=0.099), the number of chemotherapy cycles ( p=0.04) received before transplant, and the total dose of mononuclear cells infused at the time of transplant were the only variables associated with secondary MDS/AL. Autologous transplantation with progenitor cells isolated from peripheral blood after mobilization with cytokines has probability and risk factors for secondary MDS/AL development similar to bone marrow grafts when compared with other published series.

A phase II trial of 9-aminocaptothecin (9-AC) as a 120-h infusion in patients with non-small cell lung cancer.

In a previous phase II trial of the synthetic topoisomerase I inhibitor, 9-aminocamptothecin (9-AC), given as a 72-h infusion, we identified modest single agent activity of 9% in patients with previously untreated advanced non-small cell lung cancer (NSCLC). Preclinical studies suggested that a more prolonged continuous infusion of the drug might lead to greater antitumor activity. A phase I study recommended a phase II dose of 25 microg/m2/hr for 120 h (3000 microg/m2 over 5 days), administered for 2 consecutive weeks of a 3-week cycle. We utilized this schedule and enrolled 13 chemotherapy-naïve patients with Stage IIIB and IV NSCLC in this trial: median age 67 (range 57-74); 46% male; 92% stage IV; and median performance status 1. Twelve patients are available for response and toxicity evaluation after 2 cycles of therapy. One patient achieved a partial response. Four patients had stable disease while seven patients had progressive disease. Patients with stable or progressive disease after two cycles received no additional 9-AC, and were offered conventional chemotherapy. The median survival time was 10.2 months and the one-year survival rate 28% (95% confidence interval, 5-58%). Significant toxicities included myelosuppression, fatigue, and anorexia. One patient had grade 4 neutropenia following the first week of cycle 2, and did not receive additional therapy. There were no neutropenia-related infections. These data suggest that this prolonged schedule is unlikely to increase 9-AC's very modest activity in NSCLC above that seen with the simpler 72-h administration schedule. Further evaluation of 9-AC in NSCLC is not recommended.

Identification of factors associated with poor peripheral blood progenitor cell mobilization in Hodgkin's disease.

BACKGROUND AND OBJECTIVES: Although the use of drugs which damage stem cells is common in patients with Hodgkin's disease (HD), factors affecting peripheral blood progenitor cell (PBPC) mobilization have not been clearly established in this group of patients. The aim of this study was to identify factors associated with poor PBPC mobilization in patients with HD. DESIGN AND METHODS: In order to address this issue we have evaluated in 54 patients with HD mobilized with G-CSF alone the following factors: sex, age, histologic subtype, B symptoms at diagnosis, status of remission, previous chemotherapy and radiotherapy, interval from diagnosis and last chemotherapy cycle to harvest, and dose of G-CSF. Univariate analysis was performed using Student's t-test, Pearson's correlation and Spearman's correlation. A stepwise regression model was used to determine which of the variables was the most predictive of PBPC mobilization. RESULTS: In univariate analysis poorer PBPC mobilization was observed in patients who had previously received at least two courses of mini-BEAM (p=0.006), a high number of different chemotherapy regimens (p=0.002), a chemotherapy score >30 (p=0.02) and more than 9 months of alkylating agents (p=0.07). We did not find radiotherapy to be a significant factor affecting progenitor cell yield (p=0.59). In the stepwise regression model, only the previous administration of two or more mini-BEAM cycles predicted a poor PBPC yield (p=0.006). INTERPRETATION AND CONCLUSIONS: Previous chemotherapy, principally exposure to a mini-BEAM regimen, seems to be the principal factor affecting collection of PBPC in patients with HD mobilized with G-CSF alone. Since mini-BEAM is an effective salvage regimen in relapsed or refractory HD, collection of PBPC should be planned when there has been no or only minimal exposure to a mini-BEAM regimen.

Donor age-related differences in PBPC mobilization with rHuG-CSF.

BACKGROUND: Data on the administration of rHuG-CSF to normal donors <18 years old are very limited. STUDY DESIGN AND METHODS: The results of rHuG-CSF administration to 61 donors <18 years old (Group A) were retrospectively evaluated and compared with results from 353 donors > or = 18 years old (Group B) who are included in the Spanish National Donor Registry. The mean age (range) in Group A and B was 14 (1-17) and 38 (18-71) years, respectively (p<0.001). The mean dose of rHuG-CSF was 10 microg per kg per day (range, 9-16) during a mean of 5 days (range, 4-6). Central venous access was placed more frequently in younger donors (25% vs. 6%; p<0.001). RESULTS: The mean number of CD34+ cells collected was 7.6 and 6.9 x 10(6) per kg of donor's body weight in Group A and B, respectively. Fifty-six percent of Group A donors needed only one apheresis to achieve > or = 4 x 10(6) CD34+ cells per kg versus 39 percent of Group B donors (p = 0.01). Side effects were more common in Group B (71% vs. 41%; p<0.001). CONCLUSION: The administration of rHuG-CSF to donors <18 years old leads to CD34+ cell mobilization in a pattern similar to that observed in adults. Greater age was associated with a more frequent requirement for more than one apheresis to achieve a similar number of CD34+ cells.

Factors influencing collection and engraftment of CD34+ cells in patients with breast cancer following high-dose chemotherapy and autologous peripheral blood progenitor cell transplantation.

Although autologous PBPC transplantation is being used increasingly for the treatment of breast cancer, there are few data on factors influencing mobilization and engraftment in these patients. We have analyzed these factors in 70 patients with advanced or metastatic breast cancer undergoing autologous PBPC transplantation. All patients were mobilized after stimulation with G-CSF, and a median of 3.16 x 10(6)/kg CD34+ cells (range 0.75-23.33) were infused. All patients received conditioning with a combination of cyclophosphamide, thiotepa, and carboplatin, and postinfusion G-CSF was administered to 60 patients. The median times to reach 0.5 x 10(9)/L and 1 x 10(9)/L neutrophils were 10 and 11 days, respectively. The median times to obtain 20 x 10(9)/L and 50 x 10(9)/L platelets were 12 and 18 days, respectively. An analysis of factors that influence CD34+ cell collection was performed by linear regression. Previous radiation therapy and increasing age were associated with lower numbers of CD34+ cells collected. Those variables that could influence the tempo of engraftment were examined by multivariate analysis using Cox regression models. The number of CD34+ cells infused was found to influence both neutrophil and platelet recovery. The use of G-CSF after transplant, accelerated neutrophil recovery, and having more than six cycles of previous chemotherapy was an unfavorable factor for recovering >50 x 10(9)/L platelets.

BMT: Serum Ferritin as Risk Factor for Veno-occlusive Disease of the Liver. Prospective Cohort Study.

Veno-occlusive disease of the liver (VOD) is an important complication in hematological transplantation. The aim of this study is to analyze the risk factors for VOD and other forms of liver toxicity in a cohort of 180 peripheral stem cell transplants performed in our Center. We find that elevated pretransplant levels of serum ferritin are the most important risk marker for VOD. We believe that ferritin reflects damage induced by oxygen radicals resulting from iron-mediated catalysis. We also discuss different risk factors for VOD and other forms of liver toxicity, suggesting diferent pathogenic mechanisms.

Administration of recombinant human granulocyte colony-stimulating factor to normal donors: results of the Spanish National Donor Registry. Spanish Group of Allo-PBT.

A Spanish National PBPC Donor Registry has recently been established for short- and long-term safety data collection in normal donors receiving rhG-CSF. To date, 466 donors have been included in the Registry. Median (range) dose and duration of rhG-CSF administration was 10 microg/kg/day (4-20) and 5 days (4-8), respectively. Donors underwent a median of two aphereses (range, 1-5). Adverse effects consisted mainly of bone pain (90.2%), headache (16.9%) and fever (6. 1%), but no donor discontinued rhG-CSF prematurely due to toxicity. Side-effects were more frequent in donors receiving >10 microg/kg/day than in those with lower doses (82.8% vs 61.8%; P = 0. 004). A significant decrease between baseline and post-apheresis platelet counts was the most important analytical finding (229 x 10(9)/l vs 140 x 10(9)/l; P < 0.0001), with a progressive reduction in platelet count with each apheresis procedure. One donor developed pneumothorax that required hospitalization due to central venous line placement. The mean CD34+ cell dose collected was 6.9 x 10(6)/kg (range, 1.3-36), with only 14 donors (2.9%) not achieving a minimum target of CD34+ cells of 2 x 10(6)/kg. No definitive information about potential long-term side effects is yet available. However, we hope this National Registry will serve as a useful basis for better monitoring of the efficiency and side-effects of cytokine administration in healthy people.

A prospective randomized trial of granulocyte colony-stimulating factor therapy after autologous blood stem cell transplantation in adults.

In order to assess the potential clinical benefit of filgrastim (G-CSF) after peripheral blood stem cell (PBSC) autotransplantation a randomized study was begun in our center in July 1997: 62 patients were involved (30 received filgrastim after PBSC infusion and 32, the control group, received no cytokines). All were adults (median 40 years, range 18-65). Patients with one of three different pathologies were recruited: 28 had advanced breast carcinoma, 23 had lymphomas (12 Hodgkin's disease and 11 non-Hodgkin's lymphoma) and 11 had de novo AML. All of them were transplanted using myeloablative chemotherapy conditioning regimens. G-CSF was administered subcutaneously from day +5 in the treated group at a dose of 5 microg/kg body weight/day. The numbers of CD34+ and mononuclear (MNC) cells infused were similar in each group. Only minor differences regarding the use of G-CSF could be inferred from the analysis of the data. Faster granulocyte engraftment was evident in the treated group (mean of 10 vs 12 days to achieve >0.5 x 109/l granulocytes, P = 0.0008), without differences in incidence and severity of infections, days of fever or duration of antibiotic treatment between groups. There was slightly slower platelet engraftment (mean of 15 days in the group with G-CSF vs 12 days in the other group to achieve >20 x 109/l platelets, P = NS) in this series, but there were no differences in incidence and severity of haemorrhage or platelet transfusion support. Considering the economical costs, the median expenditure per inpatient stay was Eur5961 (range Eur4386-Eur17186) in the G-CSF group compared with Eur5751 (range Eur3676-Eur15640) in the control group (P = 0.47). From our data it could be concluded that for adult patients transplanted with PBSC there is no clear beneficial impact of post-infusion G-CSF administration.

Serum Ferritin as Risk Factor for Veno-occlusive Disease of the Liver. Prospective Cohort Study.

Veno-occlusive disease of the liver (VOD) is an important complication in hematological transplantation. The aim of this study is to analyze the risk factors for VOD and other forms of liver toxicity in a cohort of 180 peripheral stem cell transplants performed in our Center. We find that elevated pretransplant levels of serum ferritin are the most important risk marker for VOD. We believe that ferritin reflects damage induced by oxygen radicals resulting from iron-mediated catalysis. We also discuss different risk factors for VOD and other forms of liver toxicity, suggesting diferent pathogenic mechanisms.