Mean structure of the supercritical turbulent spiral in Taylor-Couette flow.

The large-scale laminar/turbulent spiral patterns that appear in the linearly unstable regime of counter-rotating Taylor-Couette flow are investigated from a statistical perspective by means of direct numerical simulation. Unlike the vast majority of previous numerical studies, we analyse the flow in periodic parallelogram-annular domains, following a coordinate change that aligns one of the parallelogram sides with the spiral pattern. The domain size, shape and spatial resolution have been varied and the results compared with those in a sufficiently large computational orthogonal domain with natural axial and azimuthal periodicity. We find that a minimal parallelogram of the right tilt significantly reduces the computational cost without notably compromising the statistical properties of the supercritical turbulent spiral. Its mean structure, obtained from extremely long time integrations in a co-rotating reference frame using the method of slices, bears remarkable similarity with the turbulent stripes observed in plane Couette flow, the centrifugal instability playing only a secondary role. This article is part of the theme issue 'Taylor-Couette and related flows on the centennial of Taylor's seminal Philosophical transactions paper (Part 2)'.

Valoración del uso de la procalcitonina en el lactante febril hospitalizado / Assessing the use of procalcitonin in the hospitalised young febrile infant

INTRODUCCIÓN: El uso de la procalcitonina (PCT) se ha generalizado en la evaluación del lactante febril en urgencias. Este trabajo pretende evaluar si la introducción de la PCT ha cambiado el manejo del lactante febril hospitalizado y el coste/efectividad de dicho marcador. PACIENTES Y MÉTODOS: Estudio retrospectivo comparando 2 periodos: enero-diciembre de 2009 (sin PCT) y enero-diciembre de 2011 (uso rutinario de PCT). Se incluyó a los pacientes de 7 a 90 días de vida con fiebre ingresados en un hospital universitario y con analítica realizada. Se compararon porcentajes de infección bacteriana, uso de antibióticos, estancia hospitalaria y coste analítico. Se evaluó la PCT, la proteína-C reactiva (PCR), recuento leucocitario, score de Rochester y el lab-score propuesto por Galetto-Lacour para el diagnóstico de infección bacteriana. RESULTADOS: Se incluyó a 109 pacientes en el periodo 1 y 111 en el periodo 2 (de los cuales en 87 se dispuso de valor de PCT). La prevalencia de infección bacteriana, uso de antibióticos, repetición de analíticas y estancia hospitalaria fue similar en los 2 periodos. El coste analítico fue significativamente superior en el segundo periodo. La sensibilidad, especificidad, valor predictivo positivo y valor predictivo negativo de la PCR (punto de corte 1mg/dl) fue 70,6; 58,1; 52,6 y 75% y de la PCT (punto de corte 0,5ng/ml) 41,7; 78,4; 57,7 y 65,6%. CONCLUSIONES: El uso de la PCT no parece haber tenido un impacto significativo en el manejo del paciente hospitalizado

INTRODUCTION: The use of procalcitonin (PCT) in the evaluation of the febrile infant in the emergency care unit has been widespread. The aim of this study is to assess whether the introduction of PCT has changed the management of hospitalised febrile infants and the cost/effectiveness of this marker. MATERIALS AND METHODS: A retrospective study was performed comparing 2 periods: January-December 2009 (without PCT) and January-December 2011 (routine use of PCT). Infants aged 7 to 90 days with fever who were admitted to a university hospital and had a blood test performed were included in the study. Bacterial infection rate, antibiotic use, hospitalisation days, and analytical costs were compared. Evaluations were made using PCT, C-reactive protein (CRP), white cell count, Rochester score, and the lab-score proposed by Galetto-Lacour for the diagnosis of bacterial infection. RESULTS: A total of 109 patients were included in period 1, and 111 in period 2 (87 of which had a PCT value). The prevalence of bacterial infection, use of antibiotics, number of blood tests, and days of hospital admission was similar in both periods. The blood test cost was significantly higher in the second period. Sensitivity, specificity, positive predictive value and negative predictive value were 70.6, 58.1, 52.6 and 75%, respectively for the CRP (cut-off 1mg/dL) and 41.7; 78.4; 57.7, and 65.6% for the PCT (cut-off value 0.5ng/ml). CONCLUSIONS: The use of PCT does not seem to have a significant impact on the management of the hospitalised febrile infant

[Assessing the use of procalcitonin in the hospitalised young febrile infant]. / Valoración del uso de la procalcitonina en el lactante febril hospitalizado.

INTRODUCTION: The use of procalcitonin (PCT) in the evaluation of the febrile infant in the emergency care unit has been widespread. The aim of this study is to assess whether the introduction of PCT has changed the management of hospitalised febrile infants and the cost/effectiveness of this marker. MATERIALS AND METHODS: A retrospective study was performed comparing 2 periods: January-December 2009 (without PCT) and January-December 2011 (routine use of PCT). Infants aged 7 to 90 days with fever who were admitted to a university hospital and had a blood test performed were included in the study. Bacterial infection rate, antibiotic use, hospitalisation days, and analytical costs were compared. Evaluations were made using PCT, C-reactive protein (CRP), white cell count, Rochester score, and the lab-score proposed by Galetto-Lacour for the diagnosis of bacterial infection. RESULTS: A total of 109 patients were included in period 1, and 111 in period 2 (87 of which had a PCT value). The prevalence of bacterial infection, use of antibiotics, number of blood tests, and days of hospital admission was similar in both periods. The blood test cost was significantly higher in the second period. Sensitivity, specificity, positive predictive value and negative predictive value were 70.6, 58.1, 52.6 and 75%, respectively for the CRP (cut-off 1mg/dL) and 41.7; 78.4; 57.7, and 65.6% for the PCT (cut-off value 0.5ng/ml). CONCLUSIONS: The use of PCT does not seem to have a significant impact on the management of the hospitalised febrile infant.

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.

Usefulness and reproducibility of cytomorphologic evaluations to differentiate myeloma from monoclonal gammopathies of unknown significance.

We attempted to differentiate monoclonal gammopathies of unknown significance (MGUS) and multiple myeloma (MM) on morphologic grounds and to determine interobserver reproducibility of the differentiation. Cytologists blindly evaluated bone marrow smears from 154 patients with bone marrow plasmacytosis for the proportion of plasma cells with predefined cellular atypias. The single morphologic characteristic that most strongly differentiated MM from MGUS was the presence of nucleoli. The percentage of plasma cells, cytoplasmic contour irregularities, and anisocytosis also predicted a diagnosis of myeloma in multivariate analysis. Six cytologists independently evaluated 68 consecutive cases to determine sensitivity and specificity of these cytomorphologic features. The interobserver coefficient of variation for the plasma cell count was 33%. On consideration of the diagnosis, 36 of 41 MGUS cases and all 24 cases of myeloma were classified correctly. The use of a predesigned score system did not present such a bias, although it did not improve overall efficiency. The plasma cell count is the most predictive characteristic of myeloma from a cytologic viewpoint, but the interobserver variability is high. Interobserver variability is also high in the assessment of morphologic atypia, and atypical traits are not uncommon in plasma cells in MGUS.

Usefulness of thrombopoietin in the diagnosis of peripheral thrombocytopenias.

BACKGROUND AND OBJECTIVE: Thrombocytopenia of peripheral origin is basically due to platelet destruction or splenic sequestration. Thrombopoietin (TPO) regulates platelet production stimulating megakaryocyte proliferation and maturation. The evaluation of TPO levels may be a useful tool in the diagnosis of thrombocytopenias of unknown origin. We tried to determine the value of TPO levels in some thrombocytopenias classically considered as peripheral. DESIGN AND METHODS: Serum TPO levels and platelet counts were measured in 32 thrombocytopenic patients with liver cirrhosis (LC) and 23 with chronic hepatitis C (CHC) viral infection, in 54 patients with a clinical and serological diagnosis of autoimmune thrombocytopenic purpura (AITP), and in 88 patients infected with the human immunodeficiency virus (HIV). RESULTS: Patients with LC, AITP and HIV had lower platelet counts than patients with CHC. The degree of thrombocytopenia did not, however, correlate with the TPO levels. HIV infected patients (246+/-304 pg/mL) and AITP patients (155+/-76 pg/mL) had higher TPO levels than controls (121+/-58 pg/mL). TPO levels in patients with CHC (125+/-40 pg/mL) did not differ from those in control subjects, but were slightly decreased in patients with LC (104+/-56 pg/mL). INTERPRETATION AND CONCLUSIONS: Reduced TPO production could be involved in the development of thrombocytopenia in LC patients, but not in patients with early stages of CHC viral infection. HIV and AITP patients had slightly raised levels of TPO. As TPO levels are normal or slightly increased in most peripheral thrombocytopenias, these data alone are not sufficient to distinguish the different types of peripheral thrombocytopenia. They may, however, be a useful tool for differentiating some central and peripheral thrombocytopenias.

[Erythroblastopenia during recurrence of a thymoma associated with myasthenia gravis. Apropos of a new case]. / Eritroblastopenia en el curso de un timoma recidivante asociado a miastenia gravis: a propósito de un nuevo caso.

A new case of thymoma, myasthenia gravis and pure red cell aplasia is presented. Pure red cell aplasia came out 10 years after the diagnosis of the two other diseases in one of several relapses of metastatic thymoma with clinical signs of myasthenia. Surgery, chemotherapy and radiotherapy besides pyridostigmine treatment were used in the clinical course of the patient. A phenotypical change of medullary T lymphocytes (CD4 to CD8) was observed at the same time of pure red cell aplasia diagnosis. A dual role of medullary CD2+ T cell lymphocytes, stimulant and suppressive, over erythroid progenitor cells (BFU-E and CFU-E) was suggested by in vitro cultures.

Second bone marrow transplantation for leukemia in untreated relapse.

Seven patients with relapsed acute leukemia (4 ANLL, 3 ALL) and one with juvenile chronic myelomonocytic leukemia (JCMML) received a second BMT (BMT2). Patients were conditioned with CY/TBI (n = 7) or BU/CY (n = 1) for the first BMT (BMT1), with adequate recovery in all and without the appearance of acute GVHD (n = 3) or with mild forms (grade I, n = 2; grade II, n = 3). Relapse after BMT1 occurred in < 6 months (n = 2), between 6 and 12 months (n = 5) and > 12 months (n = 1), and the interval from BMT1 to BMT2 was < 6 months (n = 1), from 6 to 12 months (n = 5) or > 12 months (n = 2). Conditioning for BMT2 was done in untreated relapse and included combinations of BU/CY (n = 2), CY/TBI (n = 1) or BU 1 mg/kg at intervals of 6 h by mouth on days -7 to -4 and melphalan 180 mg/m2 i.v. on day -2, with the addition of VP-16 in the patient with JCMML. Two patients died on day +11 with no evidence of residual leukemia at autopsy. Six patients engrafted, one of whom had an uneventful BMT2, but he relapsed 6 months later. The other five developed severe acute GVHD (grades III-IV), with a fatal outcome in three cases, while two responded to treatment and are currently alive in continuous CR at 12 and 36 months. All patients had received conventional prophylaxis against acute GVHD.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell function studies in long-term bone marrow culture after cell concentration and cryopreservation for autologous transplantation.

Autologous bone marrow transplantation (ABMT) is frequently used in the treatment of neoplastic diseases. It involves several manipulations in vitro that can damage the stem cells responsible for grafting. Long-term bone marrow cultures (LTBMC) reproduce the bone marrow microenvironment and support haematopoiesis in vitro for several weeks. This technique provides information on the extent of the injury of stem cells during manipulations of bone marrow cells in vitro. We studied the effect of the usual process of bone marrow cells in vitro in autologous transplantation: cell concentration and cell cryopreservation. 28 bone marrows from healthy donors and 45 from patients who had undergone ABMT were assayed in LTBMC. The cultures were initiated after manual or automatic buffy coat cell separation or after density gradient or automatic mononucleated cells suspension. Bone marrows were studied pre- and post-cryopreservation. The results show that several manipulations can disturb normal cell behaviour in LTBMC. Following automatic mononucleated cell separation and after thawing, the development of adherent cell layer in LTBMC is anomalous. These manipulations led to a delay in covering 50% of the flask surface, absence of adypocytes in adherent cell layer and absence of haemopoietic precursors in the supernatant at the 4th week of culture. The results suggest that LTBMC can be used for control of the manipulations in vitro related with ABMT.

Human long-term bone marrow culture as a prognostic factor for hematopoietic reconstitution in autologous transplantation.

Human long-term bone marrow cultures allow persistence of hematopoietic stem cells in vitro for several weeks. Abnormalities in these cultures have been observed after cell treatment for purging in vitro. In autologous transplantation trials an increase in grafting failures after purging has also been reported. These results suggest a correlation between culture behaviour and graft kinetics. We analyzed the pattern of growth in Dexter culture of the bone marrow fraction infused in 52 patients with malignant diseases and subjected to autologous transplantation. In 23 cases, bone marrow cells had previously been treated in vitro with Asta-Z 7654 (n = 7) or with monoclonal antibodies plus complement (n = 16). Some of the long-term bone marrow culture parameters seemed to correlate with grafting kinetics, mainly adherent cell layer development and persistence of committed hematopoietic progenitors (CFU-GM) in the supernatant cells. The absence of a stromal layer defined a group with very poor hematological recovery after transplantation. Nine cases were included in this group and only one patient (11%) had recovered granulocytes and platelets. However, 90% of patients whose long-term cultures displayed normal adherent cell behavior had recovered peripheral hematological values. These results suggest that long-term bone marrow cultures could be used as a prognostic factor for hematopoietic reconstitution in autologous transplantation.

Spontaneous splenic rupture as the initial manifestation of acute lymphoblastic leukaemia: immunophenotype and cytogenetics.

Spontaneous splenic rupture is a rare, though life-threatening complication of some hematological malignancies and is even more infrequent as the initial symptom of acute lymphoblastic leukemia. We describe the fourth case, to our knowledge, of acute lymphoblastic leukemia presenting as splenic rupture, and for the first time the immunophenotype and cytogenetic pattern observed.

Bone marrow purging in acute lymphoblastic leukemia: biological and clinical features.

A group of 56 patients with immunophenotyped acute lymphoblastic leukemia had their bone marrow purged using monoclonal antibody (MAb) and complement. Mononuclear marrow cells were treated with panels of MAb directed against T cells (n = 19), CD10-CALLA (n = 16), and B cells (n = 21), resulting in median specific cell depletions of 96.50, 97.59, and 96.97%, respectively. The resulting CFU-GM recoveries were 60.15, 110.6, and 72.9%. Long-term bone marrow cultures showed normal formation of adherent cell layers in 17 of 23 cases, and failure to form an adherent layer correlated with poor hematological reconstitution. A total of 32 patients (aged 4-40 years) received purged marrow grafts containing a median of 1.32 x 10(7) mononuclear cells/kg and 1.64 x 10(4) CFU-GM/kg; 7 patients required backup marrow. Time to engraftment of 500 granulocytes, 1000 leukocytes, 20,000 platelets, and 50,000 platelets was 37, 38, 39, and 57 days, respectively. A total of 16 patients (50%) remain alive and in complete remission 313-913 days posttransplant (median 565 days); 13 patients (41%) relapsed between 50 and 365 days posttransplant (median 100 days), and 3 patients (9%) died from transplant-associated complications.

Successful treatment of chronic autoimmune neutropenia with cyclosporin A.

Chronic primary autoimmune neutropenia (AIN) is a distinct clinical entity seen mostly in young children, characterized by persistent neutropenia with circulating anti-neutrophil antibodies and no associated disorders known to produce AIN. Herein we report a 22-year-old male who spontaneously developed severe chronic neutropenia with recurrent episodes of high fever and oral aphthous ulcers. Laboratory evaluations detected the presence of anti-granulocyte autoantibodies directed against the NA1 neutrophil-specific antigen. Clinical, laboratory and roentgenographic testing did not reveal any disorder known to be associated with AIN. The patient' s severe neutropenia did not respond to therapy with prednisone alone, but resolved following treatment with prednisone and high-dose cyclosporin A.

High-dose chemotherapy with bone marrow rescue for treatment of Hodgkin's disease.

Between December 1st 1984 and July 1st 1991, 20 patients, 11 males and 9 females, median age 36 years (range 14-54) with Hodgkin's disease were treated with high dose chemo-radiotherapy followed by autologous bone marrow rescue. At the time of autologous bone marrow transplantation, 8 patients were in complete remission, 9 in sensitive relapse and 3 were resistant to conventional treatments. There were 3 early procedure-related deaths: 1 cardiac failure due to cyclophosphamide treatment, 1 veno-occlusive disease, and 1 patient died from CMV interstitial pneumonitis, 4 months after ABMT. Of the 17 other patients, 15 are alive, 12 in complete remission, 2 in relapse and 1 patient is not evaluable due to short-follow-up follow-up. Disease free survival is 65% at 20 months with a follow-up of 60 months. There is a trend for a better disease-free survival in patients in complete remission at the time of autologous bone marrow transplantation vs patients in sensitive relapse, although it does not reach statistical significance (80% vs 37%).

[Treatment of resistant or relapsing Hodgkin's disease with high doses of chemotherapy followed by autologous bone marrow transplant]. / Tratamiento de la enfermedad de Hodgkin resistente o en recaída con dosis altas de quimioterapia seguido de trasplante autólogo de medula ósea.

Eleven patients with Hodgkin's disease were treated with high-dose chemotherapy followed by autologous bone marrow transplantation (ABMT). Four patients were resistant to initial therapy and 7 patients had relapsed but were progressing under second or third line therapy. The median time from initial diagnosis to transplantation was 44 months (range, 16 to 82). In 9 patients pre-ABMT consisted on high-dose CVB cyclophosphamide, etoposide and carmustine) chemotherapy, one patient was treated with BACT protocol (carmustine, cytosine arabinoside, cyclophosphamide and thioguanine) and other patient was treated with high-dose of busulfan and melphalan. In 8 patients complete remission (CR) was achieved, in one the remission was partial, one failed to respond and one case was not evaluable due to early death. Among CR patients, 2 died from late toxicity, and the other 6 remain in CR off therapy, one of them more than 33 months after ABMT. High-dose therapy produce severe myelosuppression in all patients. There were 3 treatment related death: one early death due to hemorrhagic myocarditis, one veno-occlusive disease of the liver and one due to cytomegalovirus sepsis. The high complete response rate in these heavily pretreated patients suggests that there may be an indication for high-dose therapy and ABMT in earlier resistant Hodgkin's disease. Moreover under such conditions, treatment related morbidity would be expected to be lower.

[The value of the initial bone biopsy in chronic myeloproliferative syndromes. Review of 80 cases]. / Valor de la biopsia ósea inicial en los síndromes mieloproliferativos crónicos. Revisión de 80 casos.

In order to review the histological characteristics and to evaluate the presence of valuable findings for diagnostic or prognostic purposes, 80 patients diagnosed of chronic myeloproliferative syndromes (CMPS) who had undergone initial bone marrow biopsy were studied in retrospect. The patients were distributed into 26 cases of chronic myeloid leukaemia (CML), 22 of myelofibrosis (MF), 16 of polycythaemia vera (PV) and 16 of essential thrombocythaemia (ET). The histological findings in the 26 cases of CML consisted of hypercellular bone marrow with fat depletion in all cases; marked thickening of trabeculae was seen in 4 cases and neoformation-like osseous tissue in 7 others. Erythroblastic nests were found in 11 patients, eosinophilia in 23 instances, and abnormal location of immature precursor cells (ALIP) was present in 16 cases. Reticulinic fibrosis was found in 22 patients, collagen fibrosis in 6 and sinusoidal dilatation in 5 cases. Of the 22 MF patients, 8 had normal bone trabeculae, while 14 had trabecular thickening, of moderate degree in 6 cases and marked in 8. Osteoid tissue formation was observed in 21 instances; diminished or absent fat was appreciated in 19 cases. Erythroblastic nests were present in 12 instances, ALIP in 5 and eosinophilia in 14. Reticulin fibres were increased in 22 instances, collagen fibrosis was present in 18 cases, sinusoid dilatation in 12, and lymphoid follicles were seen in 4 patients. Trabecular thickening was found in 15 cases of the PV group (16 patients) and osteoid tissue formation in 2. Fatty tissue was decreased or absent in 11 instances Erythroblastic nests plus eosinophilia were seen in 15 cases, and ALIP in 2.(ABSTRACT TRUNCATED AT 250 WORDS)