PubMed Health⌕ Search

Biomedical subjects

A F Remacha

Publications and source records attributed to A F Remacha.

At least 19 recordsLinked to original sources
PubMed2004

Evaluation of immunoassays for the measurement of soluble transferrin receptor as an indirect biomarker of recombinant human erythropoietin misuse in sport.

Soluble transferrin receptor (sTfR) has been proposed as an indirect biomarker of the misuse of recombinant human erythropoietin in sport. An extended validation of four commercially available immunoassays for its measurement in serum is presented. Two ELISA techniques (ELISA1: Orion Diagnostica; ELISA2: R&D Systems), an immunoturbidimetric technique (Turbid: Roche Diagnostics), and a nephelometric technique (Nephel: Dade Behring) were investigated. Intra-laboratory precision better than 3% and correct accuracies were obtained for the Turbid and Nephel techniques using autoanalysers. Slightly worse precision (but always better than 11%) and correct accuracies were also obtained in almost all cases for the two ELISA techniques. Inter-laboratory results showed higher concordances for the ELISA procedures (intraclass correlation coefficients of 0.848 for ELISA1 and 0.973 for ELISA2 which was clearly better). Inter-technique correlations were good for the four techniques with lower dispersions found for the techniques using autoanalysers, i.e. Turbid and Nephel. While Turbid and ELISA1 results (expressed in mg/l) were comparable, results obtained with Nephel were approximately 2.7 times lower. The relationship between those three techniques was maintained when compared with ELISA2, which uses different units (nmol/l). We conclude that ELISA2 and Nephel in our hands were the most suitable techniques in terms of sensitivity, precision and accuracy, and adequacy of the calibration curve for the measurement of sTfR in real serum samples. Discrepancies observed in the results obtained with the different sTfR techniques showed that different reference standards were used and harmonization is recommended in order to obtain comparable results.

Biomarkers↗
PubMed2004

Frequent severe liver iron overload after stem cell transplantation and its possible association with invasive aspergillosis.

Iron overload is associated with free radical generation and tissue damage. Our main objective was to ascertain the frequency and severity of iron overload in a group of 59 patients who died after conventional-intensity autologous (n=24) or allogeneic (n=35) haematopoietic stem cell transplantation (HSCT). A second objective was to investigate associations between liver-iron concentration and causes of transplant-related mortality. The median age was 41 years (range, 19-66), 41 were males and 18 females. In total, 26 patients had acute leukaemia or MDS, 10 CML, 17 lymphoma, four myeloma and two aplastic anaemia. The median hepatic iron concentration (HIC) was 138 micromol/g dry weight (7.7 mg/g; range 31-631 micromol/g). In total, 4/32 (12%) patients with HIC <150 micromol/g and 10/27 (37%) with hepatic iron > or =150 micromol/g showed invasive aspergillosis at autopsy (P=0.035). This was significant in multivariate analysis (RR 9.0; 95% CI 1.6-50.3, P=0.012). In conclusion, severe iron overload is frequent in patients who die following HSCT and is associated with invasive aspergillosis.

Adult↗
PubMed2004

Clinical utility of bone marrow flow cytometry in B-cell non-Hodgkin lymphomas (B-NHL).

AIM: To determine the efficacy of flow cytometry (FC) in the assessment of bone marrow (BM) in B-cell non-Hodgkin lymphoma (B-NHL). FC is a common practice, but is far from being validated. METHODS AND RESULTS: Morphological analysis and FC immunophenotyping were performed on 421 samples. T-cell lymphomas, Hodgkin's disease, chronic lymphocytic leukaemia and hairy cell leukaemia were not included in the study. Clonality was assessed by the standard kappa/lambda/CD19 test. Aberrant immunophenotypes present in the B-cell subpopulation were also investigated. A double-step procedure was employed in all cases to increase the sensitivity of the FC procedure. Of 380 evaluable samples, 188 corresponded to follicular lymphoma (FL), 58 to diffuse large B-cell lymphoma (DLBCL), 57 to mantle cell lymphoma (MCL), seven to Burkitt's lymphoma and the remaining 70 samples to other low-grade lymphomas. Morphological marrow infiltration was found in 148 cases, and flow immunophenotyping identified 138 cases with BM involvement. A concordance between the two methods was detected in 298 cases (79%). There was a discordance in 82 cases (21%): morphology positive/FC negative in 46 cases and morphology negative/FC positive in 36 (61% of all cases with discordance were from FL). There was no difference in outcome when patients with discordances were compared with patients without discordances. CONCLUSIONS: Most samples showed concordance between morphological and FC results. FC identified BM involvement in the absence of morphological infiltration. Morphology/FC discordance seems to have no influence on the outcome of FL patients.

Bone Marrow↗
PubMed2003

Patients with biochemical iron overload: causes and characteristics of a cohort of 150 cases.

Biochemical iron overload (IO) is a frequent metabolic abnormality. It may be caused by several diseases, and data regarding the relative frequency of these are scant. A single diagnostic protocol including clinical, biochemical, and genetic data was used to diagnose the cause of biochemical IO in a group of 150 patients referred by general practitioners. Severe alterations of the HFE gene (42 patients, 28%), hepatitis C virus infection (33 patients, 22%), and dysmetabolic syndrome with iron overload (DSIO) (22 patients, 15%) emerged as the main causes, and other single causes were found in 20 patients (13%). In 19 patients (13%), multiple causes of IO were found, and in 14 patients no cause was found, 5 of whom had classical criteria of genetic hemochromatosis (GH) without HFE mutations. Transferrin saturation index (TSI) had a very low positive predictive value (0.16) for GH among patients with biochemical IO in this setting. In conclusion, 90% of patients with biochemical IO were diagnosed with a specific disorder. GH, hepatitis C infection, and DSIO were the major causes, and a large group of patients had multiple causes of IO. TSI is not a useful indicator of GH in patients referred by general practitioners.

Adult↗
PubMed2002

Enhanced risk of thrombotic disease in patients with acquired vitamin B12 and/or folate deficiency: role of hyperhomocysteinemia.

A number of studies have identified elevated levels of homocysteine (Hcy) as a risk factor for thrombosis. Given the relationship between Hcy and thrombosis, a high prevalence of thrombosis would be expected in patients with megaloblastic anemia. The aim of our study was to determine whether an acquired vitamin B12/folate deficiency is a risk factor for thrombosis. A retrospective case and control study was performed that included 193 cases with reduced levels of vitamin B12/folate. The cases were divided initially into two groups (105 with serum vitamin B12 < or =150 pmol/l and/or low red cell folate < or = 450 nmol/l and 88 with serum vitamin B12 between 150 and 200 pmol/l and/or red cell folate between 450 and 590 nmol/l). The control group consisted of 87 additional patients who had normal levels of serum vitamin B12, red cell folate, and normal renal function. Serum Hcy, thrombotic events, and risk factors were evaluated in all participants. Eight patients (9%) in the control group had had previous vascular events although only three of these events (37.5%) were observed between the vitamin study and 2 years prior to the study. In the case group, 20% of the patients had a history of thrombosis. In contrast with controls, 85% of cases suffered thrombosis between the time they were diagnosed and 2 years prior to the time they were diagnosed as showing a vitamin deficiency. Multivariate analysis demonstrated that vitamin deficiency was a significant risk factor for arterial thrombosis [adjusted odds ratio (OR) 3.3, confidence interval (CI) 1.1-10.2]. However, when hyperhomocysteinemia was included in the analysis, vitamin deficiency was no longer a risk factor, suggesting that hyperhomocysteinemia was responsible for arterial thrombotic risk in these patients (adjusted OR 2.5, CI 1.1-5.8). As a consequence of hyperhomocysteinemia, patients with acquired vitamin deficiency of vitamin B12/folate had a high risk of thrombosis. However, a more extensive study that controls risk variables and genetic factors is needed to sort out the various contributing factors.

Adolescent↗
PubMed2002

Iron overload might increase transplant-related mortality in haematopoietic stem cell transplantation.

Iron overload (IO) is associated with free radical generation and tissue damage. Our main objective was to ascertain if very high levels (VHL) of ferritin (>/=3000 microg/l) and transferrin saturation (TS) >/=100% during conditioning had an impact on overall survival (OS) and transplant-related mortality (TRM) after a haematopoietic stem cell transplantation (HSCT). Levels of ferritin and TS were measured at days -7 and -4, respectively, in 25 patients who underwent HSCT after CY/TBI. The group consisted of 20 men and five women with a median age of 40 years. Fifteen patients were autotransplanted and 10 allotransplanted. Nine of them had a diagnosis of AL, six of CML and 10 of lymphoma. Thirteen of them were in early and 12 in advanced status of disease. VHL of ferritin and TS >/=100% were associated with a decreased OS (P = 0.001 and P = 0.006, respectively) and an increased TRM (P = 0.003 and P = 0.004, respectively) in univariate survival analysis. Both variables remained significant at multivariate analysis for OS (P = 0.03 and 0.02, respectively) and TS was an independent factor for TRM (P = 0.01). Ferritin was very close to achieving statistical significance for TRM (P = 0.06) in multivariate analysis. In conclusion, VHL of ferritin and TS >/=100% at conditioning are associated with an increase in toxic deaths after transplant.

Adolescent↗
PubMed2001

Seven new mutations in the nicotinamide adenine dinucleotide reduced-cytochrome b(5) reductase gene leading to methemoglobinemia type I.

Cytochrome b(5) reductase (b5R) deficiency manifests itself in 2 distinct ways. In methemoglobinemia type I, the patients only suffer from cyanosis, whereas in type II, the patients suffer in addition from severe mental retardation and neurologic impairment. Biochemical data indicate that this may be due to a difference in mutations, causing enzyme instability in type I and complete enzyme deficiency or enzyme inactivation in type II. We have investigated 7 families with methemoglobulinemia type I and found 7 novel mutations in the b5R gene. Six of these mutations predicted amino acid substitutions at sites not involved in reduced nicotinamide adenine dinucleotide (NADH) or flavin adenine dinucleotide (FAD) binding, as deduced from a 3-dimensional model of human b5R. This model was constructed from comparison with the known 3-dimensional structure of pig b5R. The seventh mutation was a splice site mutation leading to skipping of exon 5 in messenger RNA, present in heterozygous form in a patient together with a missense mutation on the other allele. Eight other amino acid substitutions, previously described to cause methemoglobinemia type I, were also situated in nonessential regions of the enzyme. In contrast, 2 other substitutions, known to cause the type II form of the disease, were found to directly affect the consensus FAD-binding site or indirectly influence NADH binding. Thus, these data support the idea that enzyme inactivation is a cause of the type II disease, whereas enzyme instability may lead to the type I form.

Adult↗
PubMed2000

The S65C mutation in Spain. Implications for iron overload screening.

Hereditary hemochromatosis is related to mutations of the HFE gene. The role of the S65C mutation of this gene was evaluated in a Spanish population, consisting of 100 controls and 41 patients who had resulted positive to screening for iron overload. Only one patient was heterozygous for the S65C mutation, so the S65C mutation is infrequent in our area. Nevertheless, it is advisable to search for this mutation in cases with iron overload and heterozygosity for the C282Y or H63D mutations of the HFE gene.

Case-Control Studies↗
PubMed1999

Erythropoietin plus granulocyte colony-stimulating factor in the treatment of myelodysplastic syndromes. Identification of a subgroup of responders. The Spanish Erythropathology Group.

BACKGROUND AND OBJECTIVE: Anemia leading to transfusion is probably the most important problem in patients with myelodysplastic syndromes (MDS). Human recombinant erythropoietin (rHuEpo) and granulocyte colony-stimulating factor (G-CSF) have been used to treat patients with anemia of MDS, but fewer than 50% respond. The aim of this work was to evaluate the benefit of rHuEpo +/- G-CSF treatment and to isolate the response predictive variables in a group of selected patients with MDS. DESIGN AND METHODS: A non-randomized multicenter trial was carried out in 32 patients with MDS. The inclusion criteria were age >= 18 years, refractory anemia (RA) or refractory anemia with ringed sideroblasts, Hb <= 100 g/L or receiving transfusions and serum erythropoietin <= 250 U/L. These patients were treated with subcutaneous rHuEpo (300 U/kg) three times a week for 8 weeks. In the case of partial response (PR) or no response (NR) subcutaneosly administered G-CSF (1 microg/kg) three times a week was added to the rHuEpo for 8 more weeks. If the patient achieved complete response (CR) or PR in the second phase, he was included in a follow-up phase of 24 weeks in which the dose of growth factors was tapered down. Several variables, including the score published by the Scandinavian-American group, were used as possible predictive variables. RESULTS: An erythroid response was observed in 16 patients (50%); in 12 it was a CR and in 4 it was a PR. During the period of rHuEpo administration, 7 CR and 4 PR (34.4%) were documented. Of the 14 patients in whom G-CSF was added to rHuEpo, 7 (50%) responded (3 CR and 4 PR). No major side-effects associated with growth factors were observed. The multivariate analysis showed that of the different variables evaluated only the Scandinavian-American response score was significant with a relative probability of response of 11.8 (95% confident intervals: 2.5-53) when this score was > +1 (77% of cases responded). In contrast, when this score was <= 1 only 15 % of the cases responded. INTERPRETATION AND CONCLUSIONS: Use of the Scandinavian-American response score is to be recommended in a patient-oriented approach to treating MDS cases with the Epo and G-CSF. Treatment with rHuEpo and G-CSF is safe, its main drawback being its cost. However, a long-term study evaluating the regimen's cost-benefit ratio is warranted.

Adult↗
PubMed1999

Cobalamin deficiency in patients infected with the human immunodeficiency virus.

Serum vitamin B12 levels are often low in human immunodeficiency virus (HIV)-infected patients. However, only a few patients appear to have actual vitamin B12 deficiency. A low red cell folate level accompanying the low vitamin B12 level makes the presence of vitamin B12 deficiency more likely. Our experience suggests that a low red cell folate level always indicates deficiency, but does not differentiate between vitamin B12 and folate deficiency. The deoxyuridine suppression test and the assay of serum or plasma total homocysteine and/or of methylmalonic acid levels can also be useful in the identification of patients with true vitamin B12 deficiency. HIV-positive patients frequently have absorption disorders, including vitamin B12 malabsorption. However, the correlation between vitamin B12 malabsorption and serum vitamin B12 and plasma homocysteine levels is poor. Abnormalities in vitamin B12-binding proteins, which are often found in HIV-positive patients, may explain many cases of low vitamin B12 levels. Current evidence suggests that low vitamin B12 levels are more common as the HIV disease progresses. The results of vitamin B12 treatment have been disappointing thus far, including the prevention of toxicity induced by azidothymidine. The possible role of vitamin B12 treatment in the long-term survival of HIV-infected patients is at present unknown. However, it is important to identify those patients who have real vitamin B12 deficiency to treat or prevent their hematologic and/or neurological symptoms.

Acquired Immunodeficiency Syndrome↗
PubMed1998

[Atypical familial microcytosis: a familial and genetic study].

The characteristics of familiar atypical microcytosis studied during one year were evaluated. Out of 149 patients with microcytosis in whom iron deficiency was ruled out, a heterogenous beta-thalassemia was diagnosed in 72 cases, a heterozygous delta beta-thalassemia in 16 cases and a hemoglobinopathy in 3 cases. The microcytosis was related to an inflammatory anemia in 12 cases and to an hemopathy in 9 cases. An atypical microcytosis was detected in 37 patients. A familiar and molecular analysis was carried out to detect alpha-thalassemia in cases with atypical microcytosis. It was possible to complete the familiar and molecular analysis in 35 out of 37 cases, and an alpha-thalassemia was observed in 31 patients. Most cases proved to be heterozygous or homozygous-alpha 3.7-thalassemia. No patient with heterozygous alpha zero-thalassemia was found. Most cases of familiar atypical microcytosis in our country are due to -alpha 3.7-thalassemia. Bearing these findings in mind, this analysis should only be used in situations where a problem of prenatal diagnosis is present. Moreover, systematic molecular analysis of familiar atypical microcytosis could be justified if the MCV is lower than 75 fl.

Adolescent↗
PubMed1998

Serum transferrin receptor in polycythemia.

We measured serum transferrin receptor (sTfR) levels in 22 patients with polycythemia vera and in 26 cases of secondary polycythemia. In our study, raised sTfR levels in both polycythemia groups were related to iron deficiency.

Adult↗
PubMed1998

The role of serum transferrin receptor in the diagnosis of iron deficiency.

BACKGROUND AND OBJECTIVE: Iron deficiency anemia (IDA) is often associated with inflammatory disorders. The most conventional parameters of iron metabolism are therefore affected, making the evaluation of iron status difficult. Serum transferrin receptor (sTfR) levels are raised in iron deficiency but are not influenced by inflammatory changes. The aim of this study was to investigate the role of sTfR in differentiating IDA with inflammatory features. DESIGN AND METHODS: A diagnostic study of sTfR measured by immunoassay was carried out in IDA and anemia of chronic disorders (ACD). The cut-off points of sTfR and the ratio of sTfR/serum ferritin, which were obtained after comparing IDA and ACD, were applied to a group of 64 patients with mixed iron patterns (MIX) (16 with ACD and 48 with IDA). RESULTS: The best cut-off point of sTfR between IDA and ACD was 4.7 mg/L. Applying this cut-off to the MIX group, an efficiency of 87% was obtained (sensitivity 92% and specificity 81%). This level of sTfR correctly classified 53 out of 64 cases of the MIX group (83%). Using the ratio of sTfRx 100/serum ferritin, the best cut-off point was 8 (efficiency 100%), which correctly classified 62 out of 64 cases of the MIX group (97%). INTERPRETATION AND CONCLUSIONS: This study demonstrates that sTfR in conjunction with other iron parameters is very useful in iron deficiency evaluation, especially in hospital practice. Iron treatment should be considered in patients with mixed patterns of iron status, in which the diagnosis of IDA versus ACD is difficult, when the levels of sTfR exceed the cut-off point.

Anemia↗