Síndrome POEMS: Comunicación de cuatro casos / POEMS syndrome. A report of four cases

Se presentan cuatro casos de un raro síndrome paraneoplásico de una discrasia de células plamáticas compuesto por polineuropatía, organomegalia, endocrinopatía, banda monoclonal y lesiones cutáneas (POEMS). El objetivo de la comunicación de esta serie es alertar sobre diferentes formas de presentación del síndrome de POEMS para disminuir el tiempo de diagnóstico, ya que el tratamiento temprano reduce las secuelas y mejora la calidad de vida a largo plazo; también, señalar la importancia de la clasificación de la enfermedad hematológica para realizar el tratamiento específico.

Four cases of a rare paraneoplastic syndrome associated to a plasmatic cell disorder with polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin lesions (POEMS) are here reported. The purpose of the communication is to warn of different forms of presentation of POEMS syndrome to decrease the time of diagnosis, because early treatment reduces sequels and improves quality of life in the long term, also to remark the importance of classifying the hematological disease for specific treatment.

Mesotelioma pleural sarcomatoide, con diseminación masiva a peritoneo y pericardio. Un caso de autopsia / Malignant pleural mesothelioma, with generalized dissemination to peritoneum and pericardium: a descriptive autopsy report

El mesotelioma maligno es una neoplasia originada a partir de las células mesoteliales de las membranas serosas (pleura, peritoneo, pericardio y otros). Es 5 veces más frecuente en la cavidad pleural que en la peritoneal, y puede observarse en ambas por extensión directa a través del diafragma(1). Se presenta el caso de autopsia en una mujer de 83 años, sin antecedentes de exposición al asbesto, oligosintomática, con mesotelioma pleural maligno tipo sarcomatoide, en estadio avanzado (Estadio IV). El mesotelioma es una neoplasia letal, su diagnóstico a veces resulta dificultoso debido al crecimiento lento, las manifestaciones clínicas tardías y el diagnóstico en estadios avanzados. En primer lugar debe descartarse secundarismo y ante clínica e imágenes compatibles debe plantearse su diagnóstico.

Malignant mesotheliomas are tumors derived from mesothelial cells that form the serous membranes. The incidence of mesotheliomas show a rate 5 times greater in the pleural cavity than in the peritoneum; but they can be detected in both, as a result of direct invasion through the diaphragm. A case out from an autopsy is reported, of a 83 years old female patient, with no previous history of exposure to asbestos, oligosymptomatic, with malignant pleural mesothelioma of sarcomatoideal type, at an advanced stage (Stage IV). Malignant mesotheliomas are relatively rare being a highly lethal neoplasia its diagnosis is sometimes difficult because the have a gradual development and growth, with late clinical manifestions, and with diagnosis at an advanced evolutive stages. First of all, secondarism must be discarged, and in presence of compatibles images, its diagnosis must be hypothesized.

Hematopoyesis extramedular en paciente con esferocitosis hereditaria asintomática / Extramedullary hematopoiesis in patients with asymptomatic hereditry spherocytosis

En diversas patologías con alteraciones en la producción de los elementos formes de la sangre pueden desarrollarse focos de hematopoyesis extramedular en diferentes sitios. Los más frecuentes son: bazo, hígado, ganglios linfáticos, y más raramente otros órganos como: glándulas adrenales, hillios renales, cartílagos, ligamentos, tejido adiposo, timo, pulmón, mediastino y duramadre de cráneo y columna. Generalmente el proceso es difuso pero pueden formarse grandes tumores de tejido hematopoyético. Las condiciones patológicas de la médula ósea más frecuentemente asociadas a hematopoyesis extramedular son: esferocitosis hereditaria, talasemia, síndromes mieloproliferativos con fibrosis medular, ocupación medular por patologías neoplásicas. presentamos un paciente de 45 años con esferocitosis hereditaria con masas de tejido hematopoyético extramedular paravertebral mediastinal que respondieron favorablemente a la esplenectomía.

Hereditary spherocytosis (HS) is a relatively common inherited hemolytic disorder in northern Europe and in the US. The reported prevalence of HS in Western countries is 1:5000. We describe a patient 45 years old, with hereditary spherocytosis with masses of mediastinal paravertebral extramedullary hematopoietic tissue, with a favorable response to splenectomy. The medical lieterature refers some cases of extramedullary hematopoiesis as a clinical expression of hereditary spherocytosis, mainly as thoracic masses with usually paravertebral localization. HS should be distinguished from other spherocytic hermolytic anemias. Diagnosis is usually made uring infancy or in young adults, but it can be at any moment of their life, until the seventh decade of life. Ocasionally, the diagnosis is first made in old age. The clinical expression of HS is highly variable, ranging from asymptomatic condition to a severe life-threatening hemolytic anemia. Laboratory features include spherocytosis, osmotic fragility, manifestations of hemolytic disease, elevated unconjugated bilirubin and reticulocytosis. The principal diagnostic test, RBC osmotic fragility, measures the surface/volume Ratio of the cells. The treatment of choice of HS in patients with inherited spherocytosis is splenectomy, which corrects hemolytic anemia. According to he literature, cases of failure following splenectomy have been reported.

A method for multiple sequential analyses of macrophage functions using a small single cell sample

Microbial pathogens such as bacillus Calmette-Guérin (BCG) induce the activation of macrophages. Activated macrophages can be characterized by the increased production of reactive oxygen and nitrogen metabolites, generated via NADPH oxidase and inducible nitric oxide synthase, respectively, and by the increased expression of major histocompatibility complex class II molecules (MHC II). Multiple microassays have been developed to measure these parameters. Usually each assay requires 2-5 x 10(5) cells per well. In some experimental conditions the number of cells is the limiting factor for the phenotypic characterization of macrophages. Here we describe a method whereby this limitation can be circumvented. Using a single 96-well microassay and a very small number of peritoneal cells obtained from C3H/HePas mice, containing as little as <=2 x 10(5) macrophages per well, we determined sequentially the oxidative burst (H2O2), nitric oxide production and MHC II (IAk) expression of BCG-activated macrophages. More specifically, with 100 æl of cell suspension it was possible to quantify H2O2 release and nitric oxide production after 1 and 48 h, respectively, and IAk expression after 48 h of cell culture. In addition, this microassay is easy to perform, highly reproducible and more economical

Absence of peripheral blood mononuclear cells priming in hemodialysis patients

As a consequence of the proinflammatory environment occurring in dialytic patients, cytokine overproduction has been implicated in hemodialysis co-morbidity. However, there are discrepancies among the various studies that have analyzed TNF-alpha synthesis and the presence of peripheral blood mononuclear cell (PBMC) priming in this clinical setting. We measured bioactive cytokine by the L929 cell bioassay, and evaluated PBMC TNF-alpha production by 32 hemodialysis patients (HP) and 51 controls. No difference in TNF-alpha secretion was observed between controls and HP (859 ± 141 vs 697 ± 130 U/10(6) cells). Lipopolysaccharide (5 æg/ml) did not induce any further TNF-alpha release, showing no PBMC priming. Paraformaldehyde-fixed HP PBMC were not cytotoxic to L929 cells, suggesting the absence of membrane-anchored TNF-alpha. Cycloheximide inhibited PBMC cytotoxicity in HP and controls, indicating lack of a PBMC TNF-alpha pool, and dependence on de novo cytokine synthesis. Actinomycin D reduced TNF-alpha production in HP, but had no effect on controls. Therefore, our data imply that TNF-alpha production is an intrinsic activity of normal PBMC and is not altered in HP. Moreover, TNF-alpha is a product of de novo synthesis by PBMC and is not constitutively expressed on HP cell membranes. The effect of actinomycin D suggests a putative tighter control of TNF-alpha mRNA turnover in HP. This increased dependence on TNF-alpha RNA transcription in HP may reflect an adaptive response to hemodialysis stimuli

Hemocultivos: utilidad de los antibiogramas presuntivos / Blood cultures: use of presumptive antiobiograms

Mortality associated to bacteremia varies between 20 and 40 depending upon several factors, such as focus of infection, microorganism, host conditions, etc. It has also been documented that mortality may double when the patient does not receive antibiotic treatment to which the microorganism is susceptible. The objective of our work has been to determine the correlation between disk diffusion antibiogram according to NCCLS guidelines, from isolated colonies, and the one performed directly from the blood culture flask. During 1996, in the Institute of Cardiology and Cardiovascular Surgery (ICYCC) in Buenos Aires City, 81 episodes of bacteremia were studied. In every case, an antibiogram was carried out: 1) from the bottle: a- Directly (D), harvesting 20 microliters in Mueller Hinton agar, b- Diluted (d), previous centrifugation and Gram staining to adjust turbidity equivalent to 0.5 Mc Farland; 2) from isolated colonies, according to NCCLS guidelines. There were almost no major errors, except with two strains of Enterobacter cloacae versus cephalotin. The diluted method was not so convenient to read inhibition zones, especially with staphylococci. With gram-positive bacteria, the main problems appeared in the direct method with erythromycin, oxacillin and ciprofloxacin because of minor errors. With gram-negative bacteria, major errors were observed in the direct method, mainly with piperacillin (7) and to a lesser extent with piperacillin tazobactam (2). Except for imipenem, trimethoprim sulfamethoxazoie and cefotaxime, all antimicrobial agents presented minor errors with both methodologies. Based upon the high rate of minor errors, we consider it is important to confirm results obtained with the standard technique (NCCLS), considering as presumptive those results from the blood culture bottles (D and d).

Expression and biological activity of two recombinant polypeptides related to subunit 1 of the interferon-alpha receptor

Abnormal production of interferon alpha (IFN-a) has been found in certain autoimmune diseases and can be also observed after prolonged therapy with IFN-a. IFN-a can contribute to the pathogenesis of allograft rejection in bone marrow transplants. Therefore, the development of IFN-a inhibitors as a soluble receptor protein may be valuable for the therapeutic control of these diseases. We have expressed two polypeptides encoding amino acids 93-260 (P1) and 261-410 (P2) of the extracellular domain of subunit 1 of the interferon-a receptor (IFNAR 1-EC) in E. coli. The activities of the recombinant polypeptides and of their respective antibodies were evaluated using antiproliferative and antiviral assays. Expression of P1 and P2 polypeptides was achieved by transformation of cloned plasmid pRSET A into E. coli BL21(DE3)pLysS and by IPTG induction. P1 and P2 were purified by serial sonication steps and by gel filtration chromatography with 8 M urea and refolded by dialysis. Under reducing SDS-PAGE conditions, the molecular weight of P1 and P2 was 22 and 17 kDa, respectively. Polyclonal anti-P1 and anti-P2 antibodies were produced in mice. P1 and P2 and their respective polyclonal antibodies were able to block the antiproliferative activity of 6.25 nM IFN-aB on Daudi cells, but did not block IFN-aB activity at higher concentrations (>6.25 nM). On the other hand, the polypeptides and their respective antibodies did not inhibit the antiviral activity of IFN-aB on Hep 2/c cells challenged with encephalomyocarditis virus.

Cytotoxic activity of BCG-activated macrophages against L929 tumor cells is nitric oxide-dependent

The tumoricidal activity of activated macrophages has been attributed largely to the release of tumor necrosis factor (TNF), or to the production of reactive oxygen or nitrogen intermediates. The L929 tumor cell line (a murine fibroblast-like cell) when treated with actinomycin D (ActD) has been used to measure TNFa cytotoxicity. In the present study, we determined the cytotoxic activity of BCG-activated peritoneal macrophages against ActD-untreated L929 tumor cells. Furthermore, we measured the production of hydrogen peroxide (H2O2), nitric oxide (NO) and TNF by macrophages cultured in the presence or absence of L929 cells. As expected, BCG-activated macrophages produced significant amounts of H2O2 (16.0 ± 3.0 µM), TNF (512 U/ml) and NO (71.5 ± 3.2 µM). TNF (256 U/ml) and NO (78.9 ± 9.7 µM) production was unchanged in co-cultures of L929 cells with BCG-activated macrophages but H2O2 production was totally inhibited. The cytotoxic activity was dependent on NO release since L-NAME (2.5, 5.0 and 10 mM), which blocks NO synthase, inhibited the killing of L929 cells. Addition of anti-TNF (20 µg/ml) antibodies to the cultures did not affect the tumoricidal activity of macrophages. Our results indicate that macrophage-mediated killing of L929 cells is largely dependent on NO production but independent of H2O2 or TNF release

Thioglycollate-elicited murine macrophages are cytotoxic to Mycoplasma arginini-infected YAC-1 tumor cells

Macrophages are important components of natural immunity involved in inhibition of tumor growth and destruction of tumor cells. It is known that these cells can be activated for tumoricidal activity by lymphokines and bacterial products. We investigated whether YAC-1 tumor cells infected with Mycoplasma arginini stimulate nitric oxide (NO) release and macrophage cytotoxic activity. Thioglycollate-elicited macrophages from male BALB/c mice were co-cultured for 20 h with YAC-1 tumor cells infected or not with Mycoplasma arginini. The cytotoxic activity was evaluated by MTT assay and nitrite levels were determined with the Griess reagent. Thioglycollate-elicited macrophages co-cultured with noninfected YAC-1 cells showed low cytotoxic activity (34.7 ñ 8.6per cent) and low production of NO (4.7 ñ 3.1 µM NO2-). These macrophages co-cultured with mycoplasma-infected YAC-1 cells showed significantly higher cytotoxic activity (61.4 ñ 9.1 per cent; P=0.05) and higher NO production (48.5 ñ 13 µM NO2-; P=0.05). Addition of L-NAME (10 mM), an inhibitor of NO synthesis, to these co-cultures reduced the cytotoxic activity to 37.4 ñ 2per cent (P=0.05) and NO production to 3 ñ 4 µM NO2- (P=0.05). The present data show that Mycoplasma arginini is able to induce macrophage cytotoxic activity and that this activity is partially mediated by NO.

La microbiología en la transfusión sanguínea / Microbiology in blood transfusion

La familia de los Retrovirus se encuentra en el hombre y en los animales y son una causa considerable de mortalidad. Aunque se sabe que existen hace casi 100 años, su rol como agentes patógenos humano se recononoció hace aproximadamente 15 años. Su Genoma está compuesto por ARN. Los cuadro Retrovirus humanos: HIV-1, HIV-2, HTLV-1 y HTLV-II comparten cararterísticas comunes aunque se trata de entidades diferentes. Los ensayos que se utilizan para cada uno de estos virus son similares tanto en los principios como en las técnicas. En este primer apartado (I) del ensayo "Los Retrovirus" de detallará: etipatología, configuración antigénetica, respuesta inmune específica del huésped, clasificación de los métodos de diagnósticos sérico de HIV-1 y HIV-2 luego se completará el dictum mediante una lista parcial de los equipos comerciales de diagnóstico en el Anexo 1

Valoración crítica en los tests de serodiagnóstico / Critical evaluation of serumdiagnostic tests

La calidad del diagnóstico serológico es dada por la validez y confiabilidad de su resultado. La validez de estos resultados dependen de las medidas de control empleadas antes, durante y después de cada prueba. La reelevancia del diagnóstico de la infección pre o post-transfuncional lleva implícita la necesidad de establecer programas de control de calidad que eviten las consecuencias de resultados falsos positivos o falsos negativos. Los resulatados de pruebas y ensayos son índices que nos van a permitir establecer las necesidad de cambiar el algoritmo dentro de un centro de diagnóstico. En el artículo se detallan algunos de los ejercicios de que disponemos para valorar los test diagnóstico

Dos técnicas por ELISA tamizaje HIV-1/2 / Two technique by ELISA screening HIV-1/2

El eje del discurso se centra en cualificar las características de dos de las más seleccionadas técnicas de tamizaje utilizadas en el algoritmo de screening de donantes para los agentes HIV 1/2. Las técnicas son de licencia: EQUIPO A-Abbott (Recombinant HIV-1/HIV-2 Tercera Generación) EQUIPO O-Organon Teknika (VIRONOSTIKA HIV Uni-Form II)

Differences in macrophage stimulation and leukocyte accumulation in response to intraperitoneal administration of glucose/mannose-binding plant lectins

Peritoneal macrophage stimulation (rapid spreading on glass surface and hydrogen peroxide production) and inflammatory reaction (leukocyte accumulation) obtained in C3H/HeJ mice at 8 weeks of age, after a single ip injection of 10 ug concanavalin A (Con A), a lectin extracted from Canavalia ensiformits, were compared with those obtained with two other glucose/mannose-binding lectins extracted from Canavalia brasiliensis (Con Br) and Dioclea grandiflora (DGL). All lectins enhaced macrophage spreading 3-to 4-fold at 24-72 compared to control. Stimulation of hydrogen peroxide release by Con A, Con Br and DGL lasted 1,2 anmd 3 days, respectively. Leukocyte cell influx at 24-72 h after lectin injection consisted mainly of mononuclear cells. Con A induced a moderate increase in the total number of peritoneal cells,. whereas administration of Con Br or DGL increased the number of peritoneal cells 2-to 3-fold. The results indicate that DGL and Con Br have more pronounced effects on macrophage stimulation and inflammatory reactions than Con A

Superoxide-independent hydrogen peroxide release by activated macrophages

The present data show that freshly explanted BCG-activated mouse peritoneal macrophages release large quantities of hydrogen peroxide upon initial contact with a foreign substratum, without the requirement for other membrane stimuli such as phorbol diesters. The hydrogen peroxide detected under these conditions does not originate from extracellularly released superoxide, since 2 x 10**5 BCG-activated macrophages spontaneously released 1.6 nmol hydrogen peroxide but only 0.2 nmol superoxide. Thus, more than 90% of the hydrogen peroxide detected was not derived from extracellular superoxide dismutation. The dissociation between hydrogen peroxide and superoxide release was further demonstrated in cytochalasin B- or lidocaine-treated cells or in the absence of glucose. Under these conditions, hydrogen peroxide release was markedly inhibited while superoxide release was unaffected. These observations provide evidence that another metabolic pathway is involved in the generation and release of hydrogen peroxide during adherence and spreading of freshly explanted activated macrophages onto a substratum