Prognosis of patients with severe cerebral venous thrombosis treated with decompressive craniectomy.

INTRODUCTION: Despite the highly favorable prognosis, mortality occurs in nearly 2% of patients with cerebral venous thrombosis (CVT), in which decompressive craniectomy (DC) may be the only way to save the patient's life. The aim of this report is to describe the risk factors, neuroimaging features, in-hospital complications and functional outcome of severe CVT in patients treated with DC. MATERIALS AND METHODS: Consecutive malignant CVT cases treated with DC from a retrospective third-level hospital database were analyzed. Demographic, clinical, and functional outcomes were analyzed. RESULTS: Twenty-six patients were included (20 female, age 35.4±12.1 years); 53.8% of the patients had acute CVT, with neurological focalization as the most common symptom in 92.3% of the patients. Superior sagittal sinus thromboses were found in 84.6% of cases. Bilateral lesions were present in 10 patients (38.5%). Imaging on admission showed a parenchymal lesion (venous infarction±hemorrhagic lesion)>6cm measured along the longest diameter in 25 patients (96.2%). Mean duration of clinical neurological deterioration was 3.5 days; eleven patients (42.3%) died during hospitalization. CONCLUSION: In patients with severe forms of CVT, we found higher mortality than previously reported. DC is an effective life-saving treatment with acceptable functional prognosis for survivors.

Prognosis of patients with severe cerebral venous thrombosis treated with decompressive craniectomy.

INTRODUCTION: Despite the highly favorable prognosis, mortality occurs in nearly 2% of patients with cerebral venous thrombosis (CVT), in which decompressive craniectomy (DC) may be the only way to save the patient's life. The aim of this report is to describe the risk factors, neuroimaging features, in-hospital complications and functional outcome of severe CVT in patients treated with DC. MATERIALS AND METHODS: Consecutive malignant CVT cases treated with DC from a retrospective third-level hospital database were analyzed. Demographic, clinical, and functional outcomes were analyzed. RESULTS: Twenty-six patients were included (20 female, age 35.4±12.1 years); 53.8% of the patients had acute CVT, with neurological focalization as the most common symptom in 92.3% of the patients. Superior sagittal sinus thromboses were found in 84.6% of cases. Bilateral lesions were present in 10 patients (38.5%). Imaging on admission showed a parenchymal lesion (venous infarction±hemorrhagic lesion)>6cm measured along the longest diameter in 25 patients (96.2%). Mean duration of clinical neurological deterioration was 3.5 days; eleven patients (42.3%) died during hospitalization. CONCLUSION: In patients with severe forms of CVT, we found higher mortality than previously reported. DC is an effective life-saving treatment with acceptable functional prognosis for survivors.

Anaemia at admission is associated with poor clinical outcome in cerebral venous thrombosis.

BACKGROUND AND PURPOSE: Anaemia is associated with poor clinical outcome after ischaemic and haemorrhagic stroke. The association between anaemia and outcome in patients with cerebral venous thrombosis (CVT) was examined. METHODS: Consecutive adult patients with CVT were included from seven centres. Anaemia at admission was scored according to World Health Organization definitions. Poor clinical outcome was defined as a modified Rankin Scale score 3-6 at last follow-up. A multiple imputation procedure was applied for handling missing data in the multivariable analysis. Using binary logistic regression analysis, adjustments were made for age, sex, cancer and centre of recruitment (model 1). In a secondary analysis, adjustments were additionally made for coma, intracerebral haemorrhage, non-haemorrhagic lesion and deep venous system thrombosis (model 2). In a sensitivity analysis, patients with cancer were excluded. RESULTS: Data for 952 patients with CVT were included, 22% of whom had anaemia at admission. Patients with anaemia more often had a history of cancer (17% vs. 7%, P < 0.001) than patients without anaemia. Poor clinical outcome (21% vs. 11%, P < 0.001) and mortality (11% vs. 6%, P = 0.07) were more common amongst patients with anaemia. After adjustment, anaemia at admission increased the risk of poor outcome [adjusted odds ratio (aOR) 2.4, 95% confidence interval (CI) 1.5-3.7, model 1]. Model 2 revealed comparable results (aOR 1.9, 95% CI 1.2-3.2), as did the sensitivity analysis excluding patients with cancer (aOR 2.3, 95% CI 1.3-3.8, model 1). CONCLUSION: The risk of poor clinical outcome is doubled in CVT patients presenting with anaemia at admission.

The use of 185 MBq and 740 MBq of 153-samarium hydroxyapatite for knee synovectomy in haemophilia.

The penetration of beta energy of 153-samarium ((153) Sm) (0.8 MeV) is not only appropriate for synovectomy of median articulations but is possible to improve the radiobiological effect using increased activities. The aim of this study was to assess the effectiveness of 185 MBq and 740 MBq of 153-samarium hydroxyapatite ((153) Sm-HA) in knees of haemophilic patients. Thirty-one patients--36 knees, 30 males, were divided into two groups without coinjection of corticosteroid: A - 14 patients (17 knees) treated with intra-articular dose of 185 MBq of (153) Sm-HA, average age 23 years; B--17 patients (19 knees) with 740 MBq of (153) Sm-HA, average age 21.3 years. The evaluation before and after 1 year of synovectomy used the following criteria: reduction in the number of haemarthroses and use of the coagulation factor and improvement in articular motility. Adverse-effects occurrence was considered too. Early and late scintigraphic studies were performed after synoviorthesis and no joint immobilization was recommended. The reduction in haemarthrosis and use of coagulation factor were: group 1--31.3% and 25%; group 2--81.5% and 79% with P < 0.001 respectively; no significant improvement in knees motility was noted for both groups. Four cases of mild reactional synovitis were observed in each group. The scintigraphic control showed homogenous distribution of the radiopharmaceuticals with no articular escape; the material was considered safe by its permanence in the articulation. We have significant improvement in the synovectomy of haemophilic knees with 740 MBq of (153) Sm-HA; the less penetration of its beta radiation was compensated by the increased biological effect with the higher used activity.

Performance assessment of the single photon emission microscope: high spatial resolution SPECT imaging of small animal organs

The single photon emission microscope (SPEM) is an instrument developed to obtain high spatial resolution single photon emission computed tomography (SPECT) images of small structures inside the mouse brain. SPEM consists of two independent imaging devices, which combine a multipinhole collimator, a high-resolution, thallium-doped cesium iodide [CsI(Tl)] columnar scintillator, a demagnifying/intensifier tube, and an electron-multiplying charge-coupling device (CCD). Collimators have 300- and 450-µm diameter pinholes on tungsten slabs, in hexagonal arrays of 19 and 7 holes. Projection data are acquired in a photon-counting strategy, where CCD frames are stored at 50 frames per second, with a radius of rotation of 35 mm and magnification factor of one. The image reconstruction software tool is based on the maximum likelihood algorithm. Our aim was to evaluate the spatial resolution and sensitivity attainable with the seven-pinhole imaging device, together with the linearity for quantification on the tomographic images, and to test the instrument in obtaining tomographic images of different mouse organs. A spatial resolution better than 500 µm and a sensitivity of 21.6 counts·s-1·MBq-1 were reached, as well as a correlation coefficient between activity and intensity better than 0.99, when imaging 99mTc sources. Images of the thyroid, heart, lungs, and bones of mice were registered using 99mTc-labeled radiopharmaceuticals in times appropriate for routine preclinical experimentation of <1 h per projection data set. Detailed experimental protocols and images of the aforementioned organs are shown. We plan to extend the instrument's field of view to fix larger animals and to combine data from both detectors to reduce the acquisition time or applied activity.

(67)Ga and (68)Ga purification studies: preliminary results.

The positron emission tomography technique is very useful for diagnosis of several diseases. (68)Ga is a positron emitter with half-life of 67.7 min. As it is available from (68)Ge/(68)Ga generator systems, it is not necessary to have a nearby cyclotron. However, the eluate from commercial generators contains high levels of metallic impurities, which compete with (68)Ga in biomolecular labeling. Thus, a subsequent purification step is needed after generator elution. Here we present the results of two different methods developed for handmade purification of (68)Ga and (67)Ga for subsequent radiolabeling of biomolecules. Two purification methods were employed. The first one uses a cation exchange resin, and (68)Ga is eluted with a solution of acetone/acid. The second method of purification is performed by column chromatography solvent extraction, with (68)Ga recovery in deionized water. The best result was achieved with cationic resin AG50W-X8 (>400 mesh). However, the resin is not commercially available. The extraction chromatography column based on absorption of diisopropyl ether in XAD-16 is the most promising purification method. Although the levels of (68)Ga recovery and purification were smaller with the cationic resin method, its advantage is the (68)Ga recovery in deionized water.

Estabilización dinámica con ligamentoplastia interespinosa en discopatía degenerativa de columna vertebral lumbar / Dynamic stabilization with interspinous ligamentoplasty in degenerative discopaty of lumbar spine

El tratamiento de la Discopatía Degenerativa lumbar, mediante dispositivo suave de estabilización dinámica, con el uso de ligamento para reforzamiento interespinoso, altera favorablemente el movimiento y la transmisión de carga de un segmento vertebral, proporcionando estabilidad y previniendo la enfermedad del segmento adyacente. Por lo tanto se realiza un estudio prospectivo, longitudinal con 25 pacientes con edades comprendidas entre 15 y 58 años, con diagnóstico de Discopatia degenerativa lumbar; con estudios de imágenes previos con radiografias en proyección AP, lateral y laterales dinámicas además de Resonancia Magnética, con los cuales se confirmo el diagnóstico, al igual que control radiológico postoperatorio, a los que se les practico semihemilaminectomia mas discectomíamas foraminectomía mas ligamentoplastia interespinosa del segmento afectado y adyacentes. Se obtuvo como resultado mejoría clínica inmediata en la mayoría de los pacientes y con pronto reintegro a sus actividades habituales luego de la cirugía.

The treatment of lumbar degenerative discopaty, by means of a soft dynamic stabilization device, with the use of ligament for interspinous reinforcement, alter favorably the movement and load transmission of a vertebral segment, providing stability and preventing the disease of the adjacent segment. Therefore a prospectivelongitudinal study is carried out on 25 patients with ages ranging from 15 to 58 years, with a lumbar degenerative disease diagnosis; previous radiographicstudies in AP, lateral and dynamic-laterals projectionsand also Magnetic Resonance Imaging confirm the diagnosis, along with postoperative radiological controls. The patients received semi-hemilaminectomy plus discectomy plus foraminectomy plus interspinous ligamentoplasty of affected and adjacent segments. As result, inmediate clinical improvement in most patients was obtained and a soon return to their usual activities after the surgery.

Radioactive synovectomy with Yttrium9° citrate in haemophilic synovitis: Brazilian experience.

Recurrent haemarthroses leading to chronic synovitis and arthropathy remain a major cause of morbidity in patients with haemophilia. Radioactive synovectomy (RS) is considered the first choice of treatment for chronic haemophilic synovitis. The aim of this study was to evaluate the effect of RS with Yttrium(90) citrate (C-Y(90)) in the joints of patients with chronic haemophilic synovitis. From 2003 to 2007, 245 joints (118 knees, 76 elbows, 49 ankles and two shoulders) of 190 patients with haemophilia or von Willebrand disease were submitted to RS with C-Y(90) at Hemocentro de Mato Grosso, Brazil. Forty joints had radiographic Pettersson scores above 8. There were 36 joints of 22 patients with inhibitors to factor VIII. The procedure was safe with low occurrence of adverse events. The main effect was the overall reduction in joint bleeding frequency, from 19.8 to 2.6 per year post-RS. Similar results were obtained in cases with high radiographic scores and in inhibitor patients. Pain reduction was observed in most cases. Average range of motion was maintained or increased 1 year post-RS in most joints. Extension was stable or increased in 88.2% of the knees and 86.5% of the elbows. Ankle plantarflexion was stable or increased in 90.9%, whereas dorsiflexion was maintained or increased in 87.9%. Worsening of the range of motion, when present, ranged from 14 to 17 degrees. We concluded that RS with C-Y(90) represents an important resource for the treatment of chronic haemophilic synovitis, markedly reducing joint bleeding frequency and pain, irrespective of the radiographic stage and inhibitor status.

Novel cysteine proteinase in Trypanosoma cruzi metacyclogenesis.

With the aim to study proteinases released to the culture medium during Trypanosoma cruzi metacyclogenesis, the presence of cysteine proteinases (CPs) was analysed in culture supernatants obtained throughout the differentiation induced by stimulation of epimastigotes with Triatoma infestans hindgut homogenate. In SDS-gelatin containing gels, an important endopeptidase activity with apparent molecular weight range between 97 and 116 kDa was encountered at pH 6, which was abolished by the specific cysteine proteinase inhibitor E-64 and TLCK, but not by pepstatin, 1,10 phenantroline or PMSF. This novel CP, named TcCPmet, showed affinity to cystatin-Sepharose, denoting its thiol-proteinase character as well as to ConA-Sepharose, indicating it contains N-linked oligosaccharides. However, it presented a different elution pattern on ConA-Sepharose than cruzipain and, in addition, it was not recognized by anti-cruzipain serum, facts that strongly suggest the different nature of both CPs. Moroever, evidence is presented indicating that TcCPmet was able to hydrolyse the same chromogenic peptides as cruzipain at optimal alkaline pH values, although with a different order of effectiveness. Our results indicate the presence of a novel CP secreted by metacyclic trypomastigotes and reinforces the important role of these enzymes in metacyclogenesis.

[Early release of the antiinflammatory cytokine IL-10 in traumatic brain injury]. / Liberación precoz de la citokina antiinflamatoria IL10 en el trauma severo de cráneo.

It has been reported that upwards of 50% of patients who survive an initial brain traumatic insult subsequently die due to infection and multiple organ failure. A paralysis of cell-mediated immunity following trauma, partially induced by anti-inflammatory cytokine release, appears to be responsible for the increased susceptibility to infections. We determined the plasma levels of the anti-inflammatory cytokine IL-10 and the pro-inflammatory TNF-alpha in 15 patients admitted with severe traumatic brain injury (TBI). None of the patients had received glucocorticoid or catecholamine treatment. Thirteen volunteers served as controls. At study entry the IL-10 plasma levels were significantly higher than in controls: 41.8 (17.3-265.4) pg/mL vs. 2.2 (1.4-2.7) pg/mL, p < 0.001 (Mann-Whitney test). There was no difference between the first (at study entry) and second sample (4 hours later) (Wilcoxon test). TNF-alpha plasma levels were similar in patients and controls at study entry and 4 hours later. We conclude that severe TBI patients present an early response, with a significant increase of IL-10 plasma levels. These results could partially explain the immunodepression following TBI.

Liberación precoz de la citokina antiinflamatoria IL10 en el trauma severo de craneo / Early release of the antiinflammatory cytokine IL-10 in traumatic brain injury

Los pacientes que sobreviven a la injuria inicial de un trauma severo presentan con elevada frecuencia complicaciones infecciosas, sépticas y disfunción multiorgánica. Los mecanismos causales estarían relacionados a una alteración de la inmunidad celular inducida por el trauma y mediada en parte por la a expresión de citokinas antinflamatorias. Se evaluaron los niveles plasmáticos de la citokina antinflamatoria IL-10 y de la citokina proinflamatoria TNF-a en 15 pacientes ingresados con traumatismo encefalocraneano (TEC) severo predominante. Ninguno de los pacientes había recibido corticoides ni catecolaminas; 13 voluntarios normales se utilizaron como controles. Al ingreso los niveles plasmáticos de IL-10 fueron significativamente mayores en los pacientes que en los controles: 41.8 (17.3-265.4) pg/mL vs. 2.2 (1.4-2.7) pg/mL, p<0.001 (test de Mann-Withney). Los niveles de IL-10 no fueron diferentes entre la primera (menos de 6 horas post-trauma) y la segunda muestra (4 horas después) (test de Wilcoxon). Los niveles plasmáticos de TNF-a fueron semejantes en los pacientes respecto a los controles. Estos resultados muestran que los pacientes con TEC severo desarrollan precozmente una respuesta con elevación significativa de los niveles plasmáticos de IL-10 y que podría explicar, por lo menos en parte, la situación de inmunodepresión inducida por el TEC.

Receptores histamínicos H2, AMPc y diferenciación celular leucémica / H2 histaminics receptora, AMPc and leukemia celular diferenciation

Con el objeto de explorar su potencial empleo en terapéutica no citotóxicas, se estudió, en células leucémicas humanas, la vía de señalización y probable rol regulatorio del receptor a histamina H2. Mediante ensayos de binding, se detectaron sitios de unión específica de tipo H2, en casi todas las muestras de M.O.y S.P. de pacientes con L.A., con diferentes grados de infiltración. esto sugiere la presencia del receptor H2, en células hemopoyéticas normales y transformadas. La líneas U-937, modelo de célula monoblástica, presenta receptores H2, acoplados a AMPc. Su estímulo no produjo cambios proliferativos, ni deferenciación celular, pero sí un aumento transitorio, vía proteín kinasa A (PKA), en la expresión de Fos y Hun, sin reducción de Myc. Se hipotizó que el fracaso del estímulo H2, para diferenciar las células U-937 podría deberse a que su activación de la PKA es breve. Concordante con lo anterior, los receptores H2, mostraron una veloz de desensibilización homóloga (T. 1/2 = 20ï). En cambio la forskolina, un activador directo de la adenil ciclasa, no desensibilizó su estímulo ni aún después de 24 horas de incubación. La forskolina también inhibió la proliferación U-937 a las mismas concentraciones en que estimuló la síntesisde AMPc e indujo su diferenciación fagocitaria, con reducción del NBT y respuesta quimiotáctica al C5a. Conclusiones: 1) La desensibilización veloz de un receptor que transduce una señal diferenciadora, como el H2, en las células U-937, podría ser un mecanismo fisiopatogénico de la malignificación, al bloquear la recepción de estímulos madurativos por la célula neoplásica. 2) Dados estos resultados, y los efectos diferenciadores del dibutril AMPc (DBAMPc) en líneas celulares mieloides, los agentes que elevan el AMPc merecen ser valorados en la terapia de las LMA

Persistent diarrhea signals a critical period of increased diarrhea burdens and nutritional shortfalls: a prospective cohort study among children in northeastern Brazil.

Persistent diarrhea (PD; duration >/=14 days) is a growing part of the global burden of diarrheal diseases. A 45-month prospective cohort study (with illness, nutritional, and microbiologic surveillance) was conducted in a shantytown in northeastern Brazil, to elucidate the epidemiology, nutritional impact, and causes of PD in early childhood (0-3 years of age). A nested case-control design was used to examine children's diarrhea burden and nutritional status before and after a first PD illness. PD illnesses accounted for 8% of episodes and 34% of days of diarrhea. First PD illnesses were preceded by a doubling of acute diarrhea burdens, were followed by further 2.6-3.5-fold increased diarrhea burdens for 18 months, and were associated with acute weight shortfalls. Exclusively breast-fed children had 8-fold lower diarrhea rates than did weaned children. PD-associated etiologic agents included Cryptosporidium, Giardia, enteric adenoviruses, and enterotoxigenic Escherichia coli. PD signals growth shortfalls and increased diarrhea burdens; children with PD merit extended support, and the illness warrants further study to elucidate its prevention, treatment, and impact.

Interactions of dendritic cells with fibronectin and endothelial cells.

We studied the phenotypic characteristics of spontaneously migrated skin dendritic cells (sDC) and monocyte-derived dendritic cells (moDC), generated under different culture conditions, and their interactions with fibronectin (FN) and endothelial cells. Monocyte-derived dendritic cells were obtained after culturing monocytes with granulocyte-macrophage colony-stimulating factor (GM-CSF) (800 U/ml) and interleukin-4 (IL-4) (500 U/ml) with either 10% fetal bovine serum (FBS) or 10% allogeneic human serum (HS). Regardless of the type of serum used, the majority of moDC expressed human leucocyte antigen-DR (HLA-DR) and CD86. On day 5 of incubation, 20-67% of moDC cultured in the presence of HS (HS-moDC) expressed CD1a, b and c versus 94-97% when cultured in the presence of FBS (FBS-moDC). DC showed a differential gradient of adhesion to FN: FBS-moDC>HS-moDC>sDC approximately monocytes. Both FBS-moDC and HS-moDC were strongly positive for CD49e (alpha5-integrin) and CD29 (beta1-integrin) but negative for CD49d (alpha4-integrin). A monoclonal antibody (mAb) against CD49e blocked the adhesion of both types of moDC to FN. Although both FBS-moDC and HS-moDC attached to endothelium (a 76% and 63% increase, respectively), only HS-moDC were able to migrate through non-activated endothelium. Overall, these results suggest that spontaneously migrated sDC are less adherent to FN than moDC, that HS and FBS induce differences in CD1 expression, that HS-moDC are less adhesive to FN and endothelial cells but more motile than FBS-moDC, and that alpha5beta1-integrin is the molecule involved in moDC adhesion to FN.

Pattern of cytokine receptors expressed by human dendritic cells migrated from dermal explants.

Different reasons account for the lack of information about the expression of cytokine receptors on human dendritic cells (DC): (a) DC are a trace population; (b) the proteolytic treatment used to isolate DC may alter enzyme-sensitive epitopes; and (c) low numbers of receptors per cell. In the present work the expression of cytokine receptors was analysed by flow cytometry on the population of dermal DC (DDC) that spontaneously migrate from short-term culture dermal explants. DDC obtained after dermal culture were CD1alow, CD1b+, CD1c+, human leucocyte antigen (HLA)-DR+, CD11chigh, CD11b+ and CD32+. The DC lineage was confirmed by ultrastructural analysis. DDC expressed interleukin (IL)-1R type 1 (monoclonal antibody (mAb) hIL-1R1-M1; and 6B5); IL-1R type 2 (mAb hIL-1R2-M22); IL-2R alpha chain (mAb anti-Tac; and hIL-2R-M1) and IL-2R gamma chain (mAb 3B5; and AG14C). DDC did not stain for IL-2R beta chain using four mAbs recognizing two different epitopes of IL-2R beta (mAb 2R-B; Mik-beta 1; and CF1; Mik-beta 3, respectively). DDC were also positive for the cytokine binding chains (alpha chains) of IL-3R (mAb 9F5); IL-4R (mAb hIL-4R-M57; and S456C9); and IL-7R (mAb hIL-7R-M20; and R3434). DDC showed low levels of IL-6R alpha chain (mAb B-F19; B-R6; and B-E23) and its signal transducer gp130 (mAb A2; and B1). DDC strongly expressed interferon-gamma receptor (IFN-gamma R) (mAb GIR-208) and were negative for IL-8R (mAb B-G20; and B-F25). All DDC were highly positive for granulocyte-macrophage colony-stimulating factor receptor (GM-CSFR) alpha chain (mAb hGM-CSFR-M1; SC06; SC04, and 8G6) and to a lesser extent for the common beta chain of GM-CSFR, IL-3R and IL-5R (mAb 3D7). On the other hand, reactivity was not found for granulocyte colony-stimulating factor receptor (G-CSFR) (mAb hGCSFR-M1) nor macrophage colony-stimulating factor receptor (M-CSFR) (mAb 7-7A3-17) confirming the DC lineage of DDC. As previously reported for lymphoid DC, DDC expressed tumour necrosis factor receptort (TNFR) 75000 MW (mAb utr-1; hTNFR-M1; and MR2-1) but lacked TNFR 55000 MW (mAb htr-9; MR1-1; and MR1-2). In summary, DDC express receptors for a broad panel of cytokines, even receptors for cytokines whose effects on DC are still unknown (i.e. IL-2R alpha gamma; IL-6R alpha/gp 130; IL-7R alpha gamma).

Infecciones urinarias en la problacion puntarenense. / Urinary infections in the population of Puntarenas

Se estudiaron 3460 muestras de orina para analisis bacteriologico de pacientes hospitalizados y de Consulta Externa del Hospital Monsenor Sanabria en Puntarenas; encontrandose que la Escherichia coli, era la causante del 82,5% de las bacteriurias significativas.Proteus mirabilis, Staphylococcus aureus y Pseudomona auriginosa fueron otros de los germenes aislados. Al practicar la prueba de sensibilidad a los antibioticos se encontro que la Escherichia coli posee alta sensibilidad a la gentamicina (86.9%), el Staphylococcus aureus presento una mayor sensibilidad a la cefalosporina (90%). Se revisaron 74 expedientes correspondientes al 10% de los pacientes con bacteriuria significativa, de los mismos se desprende que la gentamicina, trimetoprin-sulfa y ampicilina fueron los antibioticos mas usados, en un 30%, 27% y 24% respectivamente