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.

ASCUS: comparative follow-up results related to previous SIL diagnosis.

The clinical significance of ASCUS (atypical squamous cells of undetermined significance) remains undetermined. In a variety of cases, it is possible to identify an underlying neoplastic squamous lesion. With the aim of establishing some rationale basis for management, we have evaluated the history and the follow-up of 137 woman diagnosed with ASCUS. These woman were distributed into two groups, with or without history of SIL (30 and 107 woman, respectively); 38 woman did not come to the control. In general, the rate was 30.3% for low grade SIL (squamous intraepithelial lesions) and 6.1% for high grade SIL. In both groups the rate of low and high grade SIL was similar. In our opinion, women that are diagnosed with ASCUS must be submitted to colposcopic exams independently of their history.

Serum erythropoietin and erythroid activity in vitamin B12 deficiency.

We studied erythropoiesis in 31 patients with vitamin B12 deficiency by measuring serum erythropoietin (s-Epo), serum transferrin receptor (s-TfR, taken as an index of total erythroid activity), reticulocyte count, and the reticulocyte maturation index (RMI). s-Epo and s-TfR were measured with commercial immunoassays, whereas reticulocyte count and RMI were determined by flow cytometry. s-Epo (123 +/- 196 U/L) and s-TfR (4.1 +/- 2 mg/L) levels were increased in patients with vitamin B12 deficiency. The absolute reticulocyte counts were decreased (29 +/- 18 x 10(9)/L) with a relative increase in the most immature fractions (RMI: 29.6 +/- 18%). A significant negative relationship was found between s-Epo and Hb level (r = -0.65, p < 0.0001). On the average, however, s-Epo was inappropriately low for the degree of anemia, since the observed/predicted (O/P) s-Epo ratio was 0.80 +/- 0.28 in vitamin B12 deficiency vs 1.00 +/- 0.16 in a group of patients with iron deficiency anemia. It is concluded that at least a portion of patients with vitamin B12 deficiency have serum erythropoietin levels that are inappropriately low for the degree of anemia.

Vitamin E serum levels in patients with leukemia, lymphoma and myeloma.

The serum alpha-tocopherol levels were determined in a group of 182 patients with hematological neoplasms: 87 lymphoid or myeloid leukemias, 65 lymphomas and 30 myelomas. The levels did not differ from those of controls, when compared either globally or for diagnosis. Low alpha-tocopherol serum levels were observed in 6 patients (3.3%).

[Neutrophilia in the bronchoalveolar lavage of patients with AIDS and Pneumocystis carinii pneumonia. Reflections on its prognostic value in the Spanish setting]. / Neutrofilia en el lavado broncoalveolar de pacientes con SIDA y neumonía por Pneumocystis carinii. Consideraciones sobre su valor pronóstico en nuestro medio.

The prognostic value of neutrophilia (> 5%) in bronchoalveolar lavage (BAL) in our context is studied in 21 patients with AIDS and Pneumocystis carinii pneumonia. Neutrophilia does not seem to be a good prognostic indicator in our context. We have found this condition, with a mean of 6 +/- 4%, in only 33% of our sample. The sensitivity of this parameter with respect to risk of death was very low (25%), while specificity was moderate (65%). In contrast with what has been reported in studies done with Anglo-Saxon populations, neutrophilia in BAL is probably of little prognostic use in our context. This may be due to various factors, among them the type of population (most being intravenous drug users) and the therapeutic protocol (early empirical treatment).

Prevalence of high serum and red cell ferritin levels in HIV-infected patients.

We report a high prevalence of elevated serum and red cell ferritin (SF and RCF) levels in 168 patients with HIV infection. SF levels increase with clinical worsening of infection and with decreasing CD4+ lymphocyte counts (ANOVA, p < 0.001) while RCF is significantly higher in asymptomatic AIDS patients (ANOVA, p < 0.001) and in those treated with zidovudine (AZT) (ANOVA, p < 0.001). It is suggested that, although inflammatory processes may explain high SF levels, if we also take in account RCF levels a possible association between iron overload and HIV infection might exist, and this may be worsened by AZT treatment. The significance of these high ferritin levels and their effects on immune system suppression and susceptibility to infectious and neoplastic complications in these patients merits further investigation.

[Hematologic changes induced by exertion during a long-distance race]. / Cambios hematológicos inducidos por el ejercicio durante una carrera de largas distancias.

PURPOSE: To evaluate the haematological changes induced by a long-distance race in well trained runners. PATIENTS AND METHODS: The haematological changes presented by 17 runners (15 men and 2 women) were assessed in a 6-hour race. For this purpose samples were examined before the race, 2 hours later, 4 hours later, at the end of the race, and 4 days after the trial. RESULTS: Haemoglobin rates, as well as leucocyte, neutrophil, monocyte and platelet counts were increased, probably due to decreased plasma volume. Haemolytic traits were seen as well, namely, increased reticulocyte count and decreased haptoglobin. High transferrin-transport capability and serum B12 levels were also present. Mild haematuria was found without any haemosiderinuria, siderinuria or haemoglobinuria. All these changes recovered in the post-race study. CONCLUSION: Changes in the major haematologic values are present during long-distance races, some of them due to haemoconcentration. Leucocytosis, haemolysis and haematuria are noteworthy, and these findings must be borne in mind when evaluating the health of runners.

Vitamin B12 transport proteins in patients with HIV-1 infection and AIDS.

BACKGROUND: Low vitamin B12 levels (B12) are often observed in patients infected with human immunodeficiency virus type 1 (HIV-1). The causes underlying this finding are thought to be intestinal malabsorption and/or abnormalities in the vitamin plasma binding proteins (BP). MATERIAL AND METHODS: Serum levels of B12 and BP were studied in eighty HIV-1-positive patients, 55 of whom met the diagnostic criteria for AIDS. Subjects were divided into various subgroups: non-AIDS HIV-1 positive versus AIDS; low serum B12 levels (DB12, < 150 pmol/L) versus normal serum B12 levels (NB12); and the results obtained were compared both between groups and with respect to a reference population (RF) of normal volunteers. RESULTS: Low levels of serum B12 were found in 14 patients (17.5%), without differences between the AIDS and non-AIDS subgroups. The levels of holohaptocorrin (holoHP) were lower in the DB12 group than in the NB12 and RF groups (p < 0.01), and no differences were found between the AIDS and non-AIDS groups. The levels of apotranscobalamin (apoTC) were higher in the AIDS group than in the non-AIDs and RF subjects (p < 0.01), but no differences were found between the DB12 and NB12 groups. Likewise, no differences were noted in the levels of holoTC between the DB12 and NB12 groups. A positive correlation between neutrophil counts and free serum haptocorrin levels (apoHP) (rs = 0.36; p = 0.002), and a negative one between the former and the levels of apoTC (rs = -0.3; p = 0.009) were observed. Furthermore, a positive correlation was detected between the erythrocyte sedimentation rate and the levels of apoHP and TC. CONCLUSIONS: Low serum levels of HP in HIV-1 positive patients could lead to the low levels of serum vitamin B12 frequently observed in this patient population, while the high levels of TC could merely represent a non-specific marker of inflammation (acute phase, reactant).

Erythroid abnormalities in rheumatoid arthritis: the role of erythropoietin.

Erythroid alterations were studied in 136 patients with rheumatoid arthritis (RA). Anemia was present in 75 cases. A definite diagnosis was determined in 65. The most frequent anemia was that of chronic disease (ACD) (43 cases); 14 patients with ACD presented with moderate to severe anemia. Prevalence of deficiencies were also high (15 cases had iron deficiency anemia, IDA). Serum erythropoietin levels were different in patients with RA compared with a healthy control group (p < 0.00001). Serum erythropoietin was increased in ACD (49 +/- 28.8 U/l) with respect to both RA (38.6 +/- 12.7 U/l, p = 0.0036) and controls (18.2 +/- 7.6 U/l, p < 0.00001). Although hemoglobin (Hb) was similar in ACD and IDA, serum erythropoietin in ACD was lower than in IDA (p = 0.01). There was a negative relationship between Hb and serum erythropoietin in ACD (r = -0.42, p = 0.005). In conclusion, almost 50% of patients with RA have anemia and ACD is the most frequent. As serum erythropoietin in ACD is blunted, patients with moderate to severe ACD are possible candidates for erythropoietin treatment.

Congenital intrinsic factor deficiency in a Spanish patient.

Vitamin B-12 deficiency was diagnosed in a 26-year-old man. Examinations performed to determine the etiology of the deficiency showed a vitamin B-12 malabsorption in the Schilling test which was corrected by adding intrinsic factor (IF) as well as normal gastric mucosa and acid secretion, although IF in gastric juice was absent. Family study showed normal serum vitamin B-12 levels in the parents, who are first cousins, and siblings. A gastric examination in the father and the sister showed decreased IF secretion, indicating heterozygosity for the disorder.

[Pernicious anemias with subtle or atypical presentation]. / Anemias perniciosas de presentación sutil o atípica.

PURPOSE: To assess the prevalence and clinico-biologic characteristics of pernicious anaemia (PA) showing subtle or atypical onset. MATERIAL AND METHODS: One-hundred and twenty-four patients were found to fulfill criteria for PA (serum vitamin B12 deficiency due to absence of intrinsic factor secretion because of severe gastric atrophy). Of them were disclosed those lacking macrocytosis (MCV less than 98 fL), with or without anaemia (Hb less than 120 g/L in women and less than 14 f/L in men), but showing decreased serum B12 rates (less than 150 pmol/L). RESULTS: Macrocytosis was absent in 15 out of the 124 cases (12.1%); either they had anaemia or not, serum B12 rates were decreased in all cases. Eight patients had concurrent iron deficiency, one had secondary anaemia, two had polycythaemia and four were normal from a haematological standpoint. Serum B12 assays were performed because of neuropsychiatric impairment (2 cases), polycythaemia study (3 cases), or positive anti-parietal cell antibodies found in an immunologic study (4 cases). The remaining patients were studied for chronic atrophy of the gastric mucosa (2 cases), and Plummer-Vinson syndrome, leucopenia and nutritional assessment (1 case of each condition). CONCLUSIONS: Atypical presentation of pernicious anaemia, whose frequency is probably underestimated, was confirmed in our environment. This condition must be suspected and ruled out in patients with characteristics similar to those described above.

Vitamin B-12 abnormalities in HIV-infected patients.

A prospective study of 60 consecutively admitted patients with HIV infection was performed to document the prevalence, etiology and manifestations of low serum vitamin B-12 in such patients. Low serum B-12 levels were found in 10 patients (16.7%). In 6, vitamin B-12 absorption was impaired and hog intrinsic factor addition did not improve it. Patients with low vitamin B-12 levels showed lower hemoglobin, leukocytes, lymphocytes, CD4 lymphocytes and CD4/CD8 lymphocyte ratio than HIV patients with physiological serum vitamin B-12 levels. However, bone marrow megaloblastosis was found in only 3 low vitamin B-12 patients and the deoxyuridine suppression test was pathological in only 1 case. In 7 patients, parenteral treatment was begun with variable response despite serum vitamin B-12 correction. In conclusion, low serum vitamin B-12 is often found in HIV-infected patients and it could be related to malabsorption, but clear megaloblastic abnormalities and treatment response could not be demonstrated. A decreased concentration of the serum binders due to disturbances in the leukocytes and related immunocompetent cell may play an additional role.