[Non-invasive ventilation in patients with diaphragmatic paralysis. Case report]. / Utilización de la ventilación no invasiva en pacientes con parálisis diafragmética. Reporte de casos.

Background Diaphragmatic paralysis (DP) is a rare disease, usually secondary to systemic processes, although idiopathic forms have been described. Aim To describe the use of non-invasive ventilation as a treatment to patients with DP. Material and methods Descriptive study about consecutive cases of DP in a general hospital. Results It has been described 4 patients, all of them with a diminished the maximum mouth pressures and vital capacity in supine position. Three patients presented hypercapnia, and one of them, required intubation with invasive mechanical ventilation. All patients were treated with non-invasive positive pressure (NPPV) mode S/T bilevel, allowing with a reduction in the PCO2, improvement in the symptoms and in the parameters to the nocturnal respiratory polygraphy. Conclusions Use of NPPV in patients with DP could provide a clinical improvement and contributing to recovery of lung functionality that make it recommendable in selected cases.

Difference between apnea-hypopnea index (AHI) and oxygen desaturation index (ODI): proportional increase associated with degree of obesity.

PURPOSE: Obesity is one of the main predisposing factors for obstructive sleep apnea (OSA) hypopnea syndrome. It has been described that body mass index (BMI) influences the accuracy of oxygen desaturation index (ODI) for the diagnosis of OSA by polysomnography (PSG). We analyzed the relationship between traditional indicators: apnea-hypopnea index (AHI) and ODI in a population at high risk for OSA, by respiratory polygraphy (RP) and PSG. METHODS: This is a retrospective study of 1898 patients with suspicion of OSA, from which 1053 underwent RP and 582 underwent PSG with OSA. We compared results considering gender, age, and degree of obesity. RESULTS: This study included 1333 records of patients with OSA-more than 80 % of whom were overweight or obese. We observed that AHI and ODI increased progressively with obesity grade and said increase was associated with BMI only in men. The evaluation of the agreement between AHI and ODI found a difference between normal weight and obese patients, regardless of gender. CONCLUSIONS: Study findings contribute to understand the role of oximetry in the diagnosis of OSA in obese patients. Our results were observed using full PSG and a simplified home method. The correlation between these indicators could improve our clinical interpretation of OSA severity among obese patients when abbreviated tests are used.

Histidine-rich glycoprotein and idiopathic pulmonary fibrosis.

Histidine-rich glycoprotein (HRG) is an enigmatic glycoprotein able to interact with a variety of ligands such as IgG, complement components, heparan sulfate, thrombospondin, fibrinogen and plasminogen. HRG is present at high concentrations in plasma and there is evidence indicating that it is able to modulate the course of biological processes such as angiogenesis, fibroblast proliferation, complement activation, coagulation and fibrinolysis. Because these processes are involved in the pathogeneses of lung fibrosis we here analyzed a possible link between HRG and idiopathic pulmonary fibrosis (IPF). We found that plasma concentrations of HRG are significantly diminished in IPF patients compared to healthy subjects. Moreover, we found a positive correlation between HRG plasma levels and forced vital capacity (FVC) values, suggesting that plasma concentration of HRG would be a useful indicator of disease activity in IPF. HRG has been described as a negative acute phase reactant able to accumulate at sites of tissue injury. Hence, we also measured the concentrations of HRG in BAL samples from IPF patients. We found that the concentrations of HRG in samples from IPF patients were significantly higher compared to controls, suggesting that the reduced concentration of HRG in plasma from IPF patients could be due, at least in part, to an enhanced uptake of this protein in the lung.

The Signature Program: Bringing the Protocol to the Patient.

Early-phase clinical development in oncology has evolved dramatically with the deciphering of the human genome in 2004. Genomic analysis and the tools identifying genetically disrupted pathways within a patient's tumor have been a driving force for personalized medicine and for the development of highly targeted novel therapies. Tumors are often genetically heterogeneous, with multiple concurrent genetic abnormalities. On the other hand, tumors arising from different tissues may share identical molecular drivers.

Use of ultrasound to prepare lipid emulsions of lorazepam for intravenous injection.

Lipid emulsions can be used as a vehicle for the production of low-volume injectable preparations with minimally water-soluble active ingredients. First, we focus on the galenic and technological conditions established by ultrasound techniques. A 2(5) factorial design was used to optimize the carrier emulsion. The study then deals with the development of a parenteral emulsion formulation for lorazepam (1 mg/ml), which is compared with the highest concentration (0.05 mg/ml) achieved in the optimal aqueous diluent for lorazepam (dextrose 5% in water). The physical and chemical stability of lorazepam in the emulsion was examined for 7 months.

[Early erythropoietin use for the prevention of anemia in infant premature]. / Uso precoz de la eritropoyetina en la prevención de la anemia del prematuro.

BACKGROUND: Anemia is common among very low birth weight newborns and requires frequent blood transfusions. Erythropoietin was been reported to be useful in the prevention of this anemia. AIM: To assess the benefits of early (before the third week of life) Human recombinant Erythropoietin (r-EPO) administration to reduce the requirement of blood transfusions in very low birth weight newborns. PATIENTS AND METHODS: Sixty newborns under 1500 g of birthweight were randomly assigned to receive r-EPO (n = 29) or placebo (n = 31) three times per week, during four weeks. Packed red cell volume and reticulocyte counts were measured weekly. Serum erythropoietin was measured prior to eighth dose. Transfusion requirements were recorded. RESULTS: r-EPO reduced transfusions from 1.41 +/- 1.1 to 0.69 +/- 1 transfusions/newborns (p < 0.001). At the fourth week of treatment, reticulocyte count was 14.8 +/- 7 and 6.4 +/- 4.9% in the active treatment group and placebo group respectively (p < 0.001). CONCLUSIONS: r-EPO reduces the requirement of transfusions in low birth weight infants.

Megakaryocytes and megakaryocyte progenitors in human cord blood.

Thrombocytopenia contributes significantly to morbidity in the sick term or preterm infant. However, few data exist on newborn's megakaryocytes and megakaryocyte progenitor cells (CFU-MK). We therefore studied CFU-MK in term and preterm infant cord blood and compared the results with data on CFU-MK from adult bone marrow and adult peripheral blood in a plasma clot culture with postirradiated aplastic canine serum (PIACS) as a source of megakaryocyte colony-stimulating activity. The number of CFU-MK and the number of cells per CFU-MK were counted with an immunofluorescent method at day 12. The effect of T-lymphocyte depletion on cord blood cultures for CFU-MK was studied with PIACS and a partially purified product of PIACS. We also studied individual megakaryocytes from newborns. The number and sizes of circulating megakaryocytes, isolated from adult peripheral blood and term venous cord blood by elutriation, were compared. Term and preterm cord blood contained more CFU-MK than adult peripheral blood. The numbers of CFU-MK in preterm cord blood were comparable to those in adult bone marrow. When the number of cells per colony were compared, cord blood contained significantly more cells than adult marrow CFU-MK. The depletion of T lymphocytes did not significantly change the growth of CFU-MK compared to nondepleted cultures. A substantial number of circulating megakaryocytes were obtained from venous cord blood, though they were significantly smaller than adult peripheral blood megakaryocytes. Since cord blood is easily obtained and contains large numbers of megakaryocytes and CFU-MK, it may provide a convenient model for studying the regulation of fetal megakaryocytopoiesis.

Resolution of pure red cell aplasia and lymphoma: response to intravenous gammaglobulin and combination chemotherapy.

Pure red cell aplasia (PRCA) rarely occurs in nonthymic lymphoproliferative disorders. This report describes the clinical course and therapy of a patient with a history of Sjogren syndrome who developed well-differentiated lymphocytic lymphoma associated with PRCA and severe hemolytic anemia. Life-threatening hemolytic anemia combined with the presence of multiple antibodies and lack of erythroid precursors was treated successfully with a single dose of intravenous gammaglobulin. A sustained, complete remission and normalization of the bone marrow was achieved following six courses of an aggressive chemotherapy regimen. Thus, occasionally low-grade lymphomas can produce life-threatening complications, requiring a more aggressive therapeutic intervention than those routinely applied.

Abnormal responses of myeloid progenitor cells to granulocyte-macrophage colony-stimulating factor in human cyclic neutropenia.

Granulocyte-macrophage progenitors (CFU-GM) from four patients with childhood onset cyclic neutropenia demonstrated abnormal in vitro proliferative responses to purified, recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) when examined in detailed dose-response studies. Marrow aspirate specimens were obtained for these studies from cyclic neutropenia patients (both during neutropenic nadirs and during recovery phases of cycles), from leukemia patients in remission who had received myelosuppressive chemotherapy, and from healthy normal volunteers. Nucleated marrow cells were then isolated by density-gradient centrifugation and cryopreserved to permit studies of CFU-GM from patients and controls to be carried out at the same time and in replicate. Maximum clonal growth of CFU-GM from normal subjects and from individuals recovering from drug-induced myelosuppression was elicited by 20-100 pmol/liter rhGM-CSF, and the CSF concentrations that induced half-maximal responses (ED50) were between 1.0 and 3.0 pmol/liter. In contrast, maximum growth of CFU-GM from the cyclic neutropenia patients required greater than or equal to 1.0 nmol/liter rhGM-CSF and ED50's were greater than 30.0 pmol/liter. These abnormalities in the GM-CSF responsive growth of myeloid progenitors were independent of cycle time and were most apparent with the predominantly neutrophilic 7-d CFU-GM. Moreover, differences in the growth of 14-d CFU-GM could be attributed mostly if not entirely to differences in the generation of neutrophilic colonies. These findings indicate that childhood onset cyclic neutropenia is associated with an underlying disturbance in the GM-CSF responsive growth of myeloid progenitors committed to neutrophilic differentiation.

An analysis of the multilineage production of human hematopoietic progenitors in long-term bone marrow culture: evidence that reactive oxygen intermediates derived from mature phagocytic cells have a role in limiting progenitor cell self-renewal.

To better understand the limited hematopoietic life span of human marrow "Dexter" cultures, we developed a miniaturized, two-stage culture system with which in vitro production of hematopoietic progenitors could be reproducibly detected and quantified. Light-density, gradient-separated human marrow cells were inoculated into Leighton slide tubes, and adherent ("stromal") cell layers were allowed to develop on the removable coverslips within these tubes during an initial 4 weeks of culture. Once stromal cell layers were established, cultures were irradiated (800 cGy) to eliminate all residual hematopoietic progenitors. The cultures were then recharged with autologous, cryopreserved marrow cells (enriched for BFU-E and CFU-GM) to reconstitute stem cell populations and to initiate in vitro hematopoiesis. Most progenitor cells added to irradiated cultures were no longer detectable by clonal assays within one to four days after recharge. Nonetheless, stable populations of adherent BFU-E and CFU-GM became established in these cultures within 24 to 48 hours, and when the total numbers of progenitors (adherent and nonadherent) were measured at weekly intervals thereafter, it was evident that both BFU-E and CFU-GM were generated in vitro. However, progenitor cell production declined as neutrophils and macrophages accumulated in the cultures. Moreover, with this accumulation of mature myeloid cells, increasing levels of O2- and H2O2 could be detected in the cultures, and it was found that the addition of oxidant scavengers (catalase and mannitol) to culture media enhanced the weekly expansions of progenitor cell numbers that could be measured. These findings support the conclusion that reactive O2 intermediates generated by mature myeloid cells have a role in limiting the duration and extent of hematopoietic progenitor cell self-renewal in long-term "Dexter" cultures of human marrow.

[Simultaneous determination of total and immature neutrophil C-reactive protein in normal, diseased, and infected newborn infants]. / Determinación simultánea de la proteína C reactiva cuantitativa y de neutrófilos inmaduros en recién nacidos normales, patológicos e infectados.

C. reactive protein and immature neutrophils/total neutrophils ratio are measured in 146 newborns. Three groups are considered: 37 healthy, 90 pathologic non infected and 19 bacteriologically confirmed infected newborns. Pathologies other than infection do not alter CRP nor I/T. Levels lower than 20 mg/l for CRP and 0.18 for I/T are considered normal. Both tests are considered very useful for neonatal infection diagnosis (p less than 0.001). CRP shows a higher sensitivity than I/T in neonatal infection diagnosis even in its initial period (84% versus 63%).