Microwave ablation of colorectal liver metastases: Impact of a 10-mm safety margin on local recurrence in a tertiary care hospital.

Microwave ablation (MWA) for colorectal liver metastasis (CLM) has been traditionally considered inferior to surgery due to the higher rate of local recurrence. The study investigated whether a safety margin of 10 mm can improve local control in patients undergoing surgical MWA. Surgical MWA was used to treat 53 lesions in 22 patients with CLM at our Institution from June 2012 to June 2017. The patients' mean age was 64.5 years, and the median size of the lesion was 16.5 mm (9-34 mm). MWA was associated with liver resection in 16 patients (72.7%). The median follow-up was 32.4 months. Univariate and multivariate analyses were performed to identify factors associated with tumor recurrence. Median ablation area was 36.6 mm2 (30-50 mm2). The complication rate was 22.7%. No local recurrence was observed during follow-up. Disease-free survival was 20 months (4.8-55.2 months). Univariate analysis revealed that the number of liver metastases and node-positive primary tumors were associated with tumor recurrence. Multivariate analysis revealed that node-positive primary tumor was the only factor significantly associated with tumor recurrence (p = 0.049; odds ratio, 12; 95% confidence interval, 1-143). When performed with a 10-mm safety margin, surgical MWA can lead to acceptable oncological outcomes with low morbidity. Therefore, it represents a good option in selected patients with CLM.

Synthesis, characterization, and assessment of novel sulfonated polynorbornene dicarboximides as adsorbents for the removal of heavy metals from water.

The occurrence of heavy metals in the natural aquatic systems arising from anthropogenic sources is an issue of global and environmental concern because of their extremely harmful effects to living beings even in rather low concentrations. The synthesis and ring-opening metathesis polymerization (ROMP) of novel norbornene dicarboximides bearing highly aromatic pendant groups, specifically, N-4-tritylphenyl-norbornene-5,6-dicarboximide (2a) and N-2,4,6-(triphenyl)phenyl-norbornene-5,6-dicarboximide (2b), their hydrogenation and further polymer sulfonation to render them adsorbents for the uptake of heavy metal ions from water is reported in this study. The macromolecules were characterized by means of FT-IR, 1H NMR, and thermal analysis, among others. A thoroughly kinetic and isothermal study of adsorption in single and ternary aqueous solutions of Pb2+, Cd2+, and Ni2+ was performed considering several experimental variables for instance initial metal concentration, contact time and solution pH. In general, the experimental data were adjusted more efficiently to the pseudo-second order kinetic model and to the Freundlich isotherm model, respectively. The maximum removal amounts were found to be 55.7 mg/g for Pb2+, 33.9 mg/g for Cd2+, and 10.2 mg/g for Ni2+ in the sulfonated trityl-bearing polymer 5a while those found for the sulfonated triphenyl-bearing polymer 5b were 31.5 mg/g for Pb2+, 26.6 mg/g for Cd2+, and 7.0 mg/g for Ni2+, respectively. The higher heavy metal removal capacity of polymer 5a was attributed to its also higher degree of sulfonation. The outcomes indicate that these novel sulfonic acid containing polymer-based adsorbents are effective for the uptake of heavy metallic elements from water.

Obtención de una versión IgG1 de ratón del rituximab para detectar la molécula CD20 humana / Obtaining a mouse IgG1 version of rituximab to detect the human CD20 molecule

Introducción: El rituximab, anticuerpo quimérico que reconoce la molécula CD20 humana, se ha utilizado en el tratamiento de diversos trastornos linfoproliferativos de células B. Para la selección de los potenciales beneficiarios del tratamiento con rituximab se han desarrollado técnicas que, mediante el uso de anticuerpos monoclonales, detectan la presencia del CD20 en los linfocitos de estos pacientes. Objetivo: Obtener y caracterizar un anticuerpo recombinante IgG1 de ratón específico para la molécula CD20 humana, que contenga las regiones variables del anticuerpo rituximab. Métodos: Para la expresión estable del anticuerpo recombinante se empleó la transducción lentiviral de células de embrión de riñón humano (HEK293). La caracterización inmunoquímica del anticuerpo se realizó por la técnica de Western Blot y su capacidad de reconocimiento de la molécula CD20 humana se evaluó por citometría de flujo e inmunohistoquímica. Resultados: Se obtuvo el anticuerpo 1F5 que reconoce, por citometría de flujo, la molécula CD20 en líneas celulares humanas de origen linfoide, así como en células de sangre periférica de humanos sanos y pacientes con trstornos linfoproliferativos de células B. Sin embargo, la técnica de inmunohistoquímica solo permitió detectar con este anticuerpo la molécula CD20 en tejidos frescos, no así en los embebidos en parafina. Conclusiones: Este trabajo sugiere las potencialidades del uso del anticuerpo 1F5 para las mediciones de la expresión de CD20 por citometría de flujo en pacientes con leucemias B o linfomas B avanzados en fase de leucemización. Esto complementaría los estudios para la selección apropiada de pacientes para el tratamiento con el rituximab(AU)

Introduction: Rituximab, chimeric antibody specific for human CD20 molecule, has been widely used in the treatment of several B-cell linfoproliferative disorders. For the selection of patients with the greatest potential to benefit from the therapy with rituximab, a number of techniques using monoclonal antibodies have been developed to detect the CD20 molecule. Objective: To obtain and to characterize a mouse IgG1 recombinant antibody, specific for human CD20, that contains the variable regions of rituximab. Methods: The lentiviral transduction of human embryonic kidney cells (HEK293) was used for the stable expression of the recombinant antibody. The immunochemical characterization of the antibody was performed by Western Blot and the recognition of CD20 was evaluated by immunohistochemistry and flow cytometry. Results: We generated the antibody 1F5, able to recognize by flow cytometry the CD20 molecule expressed on lymphoid human cell lines, as well as peripheral blood mononuclear cells from healthy donors and patients with B-cell lymphoproliferative disorders. However, 1F5 antibody detected the CD20 molecule on fresh tissues, but not on formalin-fixed paraffin embedded tissues,by immunohistochemistry. Conclusions: This work suggests the potential use of 1F5 antibody for the measurement of CD20 expression by flow cytometry in patients with B-cell leukemias or B-cell lymphomas in phase of leukemization. This could complement the studies to ensure the appropriate selection of patients for the treatment with rituximab(AU)

Dissemination of Goss's Wilt of Corn and Epiphytic Clavibacter michiganensis subsp. nebraskensis from Inoculum Point Sources.

Goss's wilt of corn, caused by Clavibacter michiganensis subsp. nebraskensis, has reemerged since 2006 as an economically important disease of corn in in the Midwestern United States. In 2012 and 2013, field plot studies were conducted with a pathogenic, rifampicin-resistant C. michiganensis subsp. nebraskensis isolate and a Goss's wilt-susceptible corn hybrid to monitor epiphytic C. michiganensis subsp. nebraskensis population densities and the temporal and spatial spread of Goss's wilt incidence originating from inoculum point sources. The randomized complete block trial included three treatments: noninoculated control, inoculum point sources established by wound inoculation, and inoculum point sources consisting of C. michiganensis subsp. nebraskensis-infested corn residue. Epiphytic C. michiganensis subsp. nebraskensis was detected on asymptomatic corn leaves collected up to 2.5 m away from inoculum sources at 15 days after inoculation in both years. The percentage of asymptomatic leaf samples on which epiphytic C. michiganensis subsp. nebraskensis was detected increased until mid-August in both years, and reached 90, 55, and 35% in wound-, residue-, and noninoculated plots, respectively, in 2012; and 50, 11, and 2%, respectively, in 2013. Although both growing seasons were drier than normal, Goss's wilt incidence increased over time and space from all C. michiganensis subsp. nebraskensis point sources. Plots infested with C. michiganensis subsp. nebraskensis residue had final Goss's wilt incidence of 7.5 and 1.8% in 2012 and 2013, respectively; plots with a wound-inoculated source had final Goss's wilt incidence of 16.6 and 14.0% in 2012 and 2013, respectively. Our findings suggest that relatively recent outbreaks of Goss's wilt in new regions of the United States may be the result of a gradual, nondetected buildup of C. michiganensis subsp. nebraskensis inoculum in fields.

Función renal, fibrosis sistémica nefrogénica y otras reacciones adversas asociadas a los medios de contraste basados en el gadolinio / Renal function, nephrogenic systemic fibrosis and other adverse reactions associated with gadolinium-based contrast media

La fibrosis sistémica nefrogénica es un trastorno fibrosante que afecta a pacientes con deterioro de la función renal y se asocia a la administración de medios de contraste basados en el gadolinio, empleados en la resonancia magnética. A pesar de tratarse de un grupo de fármacos que se consideraban seguros, la notificación de esta reacción adversa, potencialmente grave, supuso un punto de inflexión en las pautas de administración de estos medios de contraste. Se han intentado establecer parámetros de seguridad a fin de identificar a los pacientes con factores de riesgo por presentar insuficiencia renal. La estrecha farmacovigilancia y el rigor en la observación de las normativas actuales, con especial atención al valor del filtrado glomerular, han reducido los casos publicados relacionados con el uso de medios de contraste basados en el gadolinio. En un encuentro entre radiólogos y nefrólogos revisamos los aspectos más relevantes en la actualidad y las recomendaciones para su prevención (AU)

Nephrogenic systemic fibrosis is a fibrosing disorder that affects patients with impaired renal function and is associated with the administration of gadolinium-based contrast media used in MRI. Despite being in a group of drugs that were considered safe, report about this potentially serious adverse reaction was a turning point in the administration guidelines of these contrast media. There has been an attempt to establish safety parameters to identify patients with risk factors of renal failure. The close pharmacovigilance and strict observation of current regulations, with special attention being paid to the value of glomerular filtration, have reduced the published cases involving the use of gadolinium-based contrast media. In a meeting between radiologists and nephrologists we reviewed the most relevant aspects currently and recommendations for its prevention (AU)

Renal function, nephrogenic systemic fibrosis and other adverse reactions associated with gadolinium-based contrast media.

Nephrogenic systemic fibrosis is a fibrosing disorder that affects patients with impaired renal function and is associated with the administration of gadolinium-based contrast media used in MRI. Despite being in a group of drugs that were considered safe, report about this potentially serious adverse reaction was a turning point in the administration guidelines of these contrast media. There has been an attempt to establish safety parameters to identify patients with risk factors of renal failure. The close pharmacovigilance and strict observation of current regulations, with special attention being paid to the value of glomerular filtration, have reduced the published cases involving the use of gadolinium-based contrast media. In a meeting between radiologists and nephrologists we reviewed the most relevant aspects currently and recommendations for its prevention.

Effect of early metoprolol on infarct size in ST-segment-elevation myocardial infarction patients undergoing primary percutaneous coronary intervention: the Effect of Metoprolol in Cardioprotection During an Acute Myocardial Infarction (METOCARD-CNIC) trial.

BACKGROUND: The effect of ß-blockers on infarct size when used in conjunction with primary percutaneous coronary intervention is unknown. We hypothesize that metoprolol reduces infarct size when administered early (intravenously before reperfusion). METHODS AND RESULTS: Patients with Killip class II or less anterior ST-segment-elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention within 6 hours of symptoms onset were randomized to receive intravenous metoprolol (n=131) or not (control, n=139) before reperfusion. All patients without contraindications received oral metoprolol within 24 hours. The predefined primary end point was infarct size on magnetic resonance imaging performed 5 to 7 days after STEMI. Magnetic resonance imaging was performed in 220 patients (81%). Mean ± SD infarct size by magnetic resonance imaging was smaller after intravenous metoprolol compared with control (25.6 ± 15.3 versus 32.0 ± 22.2 g; adjusted difference, -6.52; 95% confidence interval, -11.39 to -1.78; P=0.012). In patients with pre-percutaneous coronary intervention Thrombolysis in Myocardial Infarction grade 0 to 1 flow, the adjusted treatment difference in infarct size was -8.13 (95% confidence interval, -13.10 to -3.16; P=0.0024). Infarct size estimated by peak and area under the curve creatine kinase release was measured in all study populations and was significantly reduced by intravenous metoprolol. Left ventricular ejection fraction was higher in the intravenous metoprolol group (adjusted difference, 2.67%; 95% confidence interval, 0.09-5.21; P=0.045). The composite of death, malignant ventricular arrhythmia, cardiogenic shock, atrioventricular block, and reinfarction at 24 hours in the intravenous metoprolol and control groups was 7.1% and 12.3%, respectively (P=0.21). CONCLUSIONS: In patients with anterior Killip class II or less ST-segment-elevation myocardial infarction undergoing primary percutaneous coronary intervention, early intravenous metoprolol before reperfusion reduced infarct size and increased left ventricular ejection fraction with no excess of adverse events during the first 24 hours after STEMI. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01311700. EUDRACT number: 2010-019939-35.

Detección inmunohistoquímica del receptor del factor de crecimiento epidérmico: revisión de algunos aspectos técnicos relacionados / Immunohistochemical detection of the epidermal growth factor receptor: review of some related technical aspects

Introducción: En los últimos años la inmunohistoquímica (IHQ) se ha convertido en el método más usado en la determinación de la expresión del receptor del factor de crecimiento epidérmico (REGF). La falta de control de algunos aspectos técnicos durante su determinación en muestras de tejidos fijados en formol e incluidos en parafina, como por ejemplo, la fijación tisular y el procesamiento de las muestras, la elección de un método adecuado de reanimación antigénica, el empleo de diferentes anticuerpos anti-REGF y sistemas de detección, a llegado a tal punto que la confiabilidad y reproducibilidad de la detección inmunohistoquímica de la sobreexpresión del REGF está siendo fuertemente cuestionada. Objetivo: La estandarización de estos procedimientos constituye una de las metas más perseguidas actualmente, con el objetivo de continuar empleando la sobreexpresión del REGF por IHQ como criterio de elección y predictor de la respuesta al tratamiento, sin necesidad de recurrir a técnicas más complejas para su detección, disminuyendo en gran medida a la variabilidad intra e interlaboratorios. Métodos: Revisión y determinación de la pertinencia en el control de la técnica investigativa y viabilidad de la misma. Conclusiones: La determinación de la sobreexpresión del REGF por IHQ continúa siendo el método más empleado actualmente como predictor de la respuesta a la terapia contra el receptor. La heterogeneidad de las muestras, la falta de estandarización de los procedimientos inmunohistoquímicos empleados, la existencia de numerosos protocolos con un mismo fin, así como otras fuentes de variabilidad, han conducido a la obtención de resultados poco confiables y reproducibles

Background: In recent years, immunohistochemistry (IHC) has become the most widely used method in determining the expression of epidermal growth factor receptor (EGFR). The lack of control of some technical aspects during their determination in formaldehyde fixed and paraffin embedded tissue such as tissue fixation and sample processing, the choice of a suitable antigen retrieval method, the use of different anti-EGFR antibodies and the detection systems have come to the point that the reliability and reproducibility of the imunohistochemical analysis of EGFR overexpression is being seriously questioned. Objective: The standardization of these procedures is one of most pursued goals at present, with the aim to continue using EGFR overexpression by IHC as selection criteria and predictor of treatment response, without resorting to most complex techniques for its detection, greatly diminishing the intra and inter laboratory variation. Methods: A review and determination of the relevance in the control of the investigative technique and its feasibility was made. Conclusions: The determination of EGFR overexpression by IHC continues being the most used method at present as predictor of the response to the therapy against the receptor. The heterogeneity of the samples, the lack of standardization of the most used immunohistochemical procedures, the existence of several protocols with the same goal, as well as other sources of variability have led to obtaining hardly reliable and reproducible results

Detección inmunohistoquímica del receptor del factor de crecimiento epidérmico: revisión de algunos aspectos técnicos relacionados / Immunohistochemical detection of the epidermal growth factor receptor: review of some related technical aspects

Introducción: En los últimos años la inmunohistoquímica (IHQ) se ha convertido en el método más usado en la determinación de la expresión del receptor del factor de crecimiento epidérmico (REGF). La falta de control de algunos aspectos técnicos durante su determinación en muestras de tejidos fijados en formol e incluidos en parafina, como por ejemplo, la fijación tisular y el procesamiento de las muestras, la elección de un método adecuado de reanimación antigénica, el empleo de diferentes anticuerpos anti-REGF y sistemas de detección, a llegado a tal punto que la confiabilidad y reproducibilidad de la detección inmunohistoquímica de la sobreexpresión del REGF está siendo fuertemente cuestionada. Objetivo: La estandarización de estos procedimientos constituye una de las metas más perseguidas actualmente, con el objetivo de continuar empleando la sobreexpresión del REGF por IHQ como criterio de elección y predictor de la respuesta al tratamiento, sin necesidad de recurrir a técnicas más complejas para su detección, disminuyendo en gran medida a la variabilidad intra e interlaboratorios. Métodos: Revisión y determinación de la pertinencia en el control de la técnica investigativa y viabilidad de la misma. Conclusiones: La determinación de la sobreexpresión del REGF por IHQ continúa siendo el método más empleado actualmente como predictor de la respuesta a la terapia contra el receptor. La heterogeneidad de las muestras, la falta de estandarización de los procedimientos inmunohistoquímicos empleados, la existencia de numerosos protocolos con un mismo fin, así como otras fuentes de variabilidad, han conducido a la obtención de resultados poco confiables y reproducibles(AU)

Background: In recent years, immunohistochemistry (IHC) has become the most widely used method in determining the expression of epidermal growth factor receptor (EGFR). The lack of control of some technical aspects during their determination in formaldehyde fixed and paraffin embedded tissue such as tissue fixation and sample processing, the choice of a suitable antigen retrieval method, the use of different anti-EGFR antibodies and the detection systems have come to the point that the reliability and reproducibility of the imunohistochemical analysis of EGFR overexpression is being seriously questioned. Objective: The standardization of these procedures is one of most pursued goals at present, with the aim to continue using EGFR overexpression by IHC as selection criteria and predictor of treatment response, without resorting to most complex techniques for its detection, greatly diminishing the intra and inter laboratory variation. Methods: A review and determination of the relevance in the control of the investigative technique and its feasibility was made. Conclusions: The determination of EGFR overexpression by IHC continues being the most used method at present as predictor of the response to the therapy against the receptor. The heterogeneity of the samples, the lack of standardization of the most used immunohistochemical procedures, the existence of several protocols with the same goal, as well as other sources of variability have led to obtaining hardly reliable and reproducible results(AU)

Validation of a flow cytometry based binding assay for evaluation of monoclonal antibody recognizing EGF receptor.

An ideal test used to characterize a product must be appropriate for the measurement of product quality, manufacturing consistency, product stability, and comparability studies. Flow cytometry has been successfully applied to the examination of antibodies and receptors on membrane surfaces; however, to date, the analytical validation of cytometry based assays is limited. Here we report on the validation of a flow cytometry-based assay used in the evaluation of nimotuzumab binding to cells over-expressing EGFR on cell surface. The assay was validated by examining, assay robustness, specificity, repeatability and intermediate precision. The assay was highly specific, robust for all studied factors except for cell fixation with 1% paraformaldehyde and met criteria for precision with RSD < 2%. In addition the assay has stability-indicating properties evidenced by the ability to detect changes in mAb degraded samples. Most importantly, the assay demonstrated to be useful for its intended use.

A state-level analysis of life expectancy in Mexico (1990-2006).

Using a methodology similar to that proposed by Barro & Sala-i-Martin (1995), it is found that, in the period 1990-2006, there was strong convergence among state-level life expectancy series, but a distancing in life expectancy in the Mexican Republic compared with more developed countries, especially during the new millennium. The interior convergence had taken place at the expense of the exterior; that is, not so much as a result of an improvement in living conditions in the poorer states, but more due to the low performance of the richer states. The causes of this situation are explained using the concept of 'epidemiological transition'.

Osteonecrosis asintomática de la cadera en los pacientes infectados por el virus de inmunodeficiencia humana / Asymptomatic osteonecrosis of the hip in HIV-infected patients

Introducción La osteonecrosis de la cadera (OTNC) en los pacientes infectados por el virus de inmunodeficiencia humana (VIH) se ha relacionado con el uso de corticoides, dislipidemia, alcoholismo, lipodistrofia, el tratamiento antirretroviral (ARV) y con la propia infección por VIH. El objetivo de este estudio fue evaluar la prevalencia de la OTNC asintomática en los pacientes infectados por VIH y su asociación con los distintos factores de riesgo. Métodos De un total de 1.200 pacientes de la consulta de VIH del Hospital Xeral-Cíes de Vigo, se seleccionaron aquéllos con diagnóstico de VIH previo a enero de 2006 y edad entre 20 y 70 años que acudieron a consulta entre los meses de marzo y mayo de 2008. Los pacientes diagnosticados de OTNC o con síntomas se excluyeron. Se efectuó una resonancia magnética (RM) de las caderas. Resultados Se incluyeron 97 pacientes de raza blanca, con una mediana de edad de 44 años, de los cuales 68 eran hombres. Se detectó OTNC en 4 enfermos (4,1%), 2 de éstas eran bilaterales. Los 4 pacientes eran varones, con una mediana de edad de 44,5 años. Se registraron múltiples factores de riesgo de OTNC en cada paciente. El nadir de linfocitos CD4 (p=0,034), la proporción de pacientes con estadio C (p=0,039) y el número de pacientes con tratamiento corticoideo previo (p=0,042) fueron significativamente diferentes entre los pacientes con OTNC y aquéllos con RM normal. Conclusiones La prevalencia de OTNC asintomática fue del 4,1%. Los factores de riesgo más importantes de OTNC fueron el tratamiento con corticoides, un nadir de linfocitos CD4 bajo y el diagnóstico de enfermedad definitoria de sida. El tratamiento con ARV no se asoció con osteonecrosis(AU)

Background Osteonecrosis (ON) of the hip in human immunodeficiency virus (HIV)-infected patients has been related to corticosteroid use, dyslipidemia, alcoholism, lipodystrophy, antiretroviral drug use, and HIV infection, itself. The aim of this study was to evaluate the prevalence of silent ON of the hip in HIV-infected patients and its association with several risk factors. Methods From a total of 1200 patients followed up at the HIV clinic of Xeral-Cies Hospital in Vigo (Spain), we selected those diagnosed with HIV infection before January 2006, aged 20–70 years, who came to the clinic during the period of March to May 2008. Patients with a diagnosis of ON of the hip and those with current symptoms were excluded. A magnetic resonance imaging (MRI) study of the hips was performed. ResultsNinety-seven Caucasian patients (68 men) with a median age of 44 years were included. ON of the hip was detected in 4 patients (4.1%), with bilateral involvement in 2 patients. All 4 patients were men, with a median age of 44.5 years. Several risk factors for ON of the hip were recorded in each patient. CD4 lymphocyte nadir (P=0.034), percentage of patients with CDC stage C (P=0.039), and number of patients with previous corticosteroid treatment (P=0.042) were significantly different between patients with ON of the hip and those with normal MRI findings. Conclusions The prevalence of asymptomatic ON of the hip in HIV-infected patients was 4.1%. The most important risk factors for developing this condition were corticosteroid treatment, lower CD4 lymphocyte nadir, and AIDS-defining disease. Antiretroviral treatment was not associated with osteonecrosis(AU)

[Asymptomatic osteonecrosis of the hip in HIV-infected patients]. / Osteonecrosis asintomática de la cadera en los pacientes infectados por el virus de inmunodeficiencia humana.

BACKGROUND: Osteonecrosis (ON) of the hip in human immunodeficiency virus (HIV)-infected patients has been related to corticosteroid use, dyslipidemia, alcoholism, lipodystrophy, antiretroviral drug use, and HIV infection, itself. The aim of this study was to evaluate the prevalence of silent ON of the hip in HIV-infected patients and its association with several risk factors. METHODS: From a total of 1200 patients followed up at the HIV clinic of Xeral-Cies Hospital in Vigo (Spain), we selected those diagnosed with HIV infection before January 2006, aged 20-70 years, who came to the clinic during the period of March to May 2008. Patients with a diagnosis of ON of the hip and those with current symptoms were excluded. A magnetic resonance imaging (MRI) study of the hips was performed. RESULTS: Ninety-seven Caucasian patients (68 men) with a median age of 44 years were included. ON of the hip was detected in 4 patients (4.1%), with bilateral involvement in 2 patients. All 4 patients were men, with a median age of 44.5 years. Several risk factors for ON of the hip were recorded in each patient. CD4 lymphocyte nadir (P=0.034), percentage of patients with CDC stage C (P=0.039), and number of patients with previous corticosteroid treatment (P=0.042) were significantly different between patients with ON of the hip and those with normal MRI findings. CONCLUSIONS: The prevalence of asymptomatic ON of the hip in HIV-infected patients was 4.1%. The most important risk factors for developing this condition were corticosteroid treatment, lower CD4 lymphocyte nadir, and AIDS-defining disease. Antiretroviral treatment was not associated with osteonecrosis.

Oligomeric proanthocyanidin complexes (OPC) exert anti-proliferative and pro-apoptotic effects on prostate cancer cells.

BACKGROUND: Oligomeric proanthocyanidin complexes (OPC) are extracted from grape seeds or maritime pine bark and have been used for enhancement of capillary stability and lymphatic drainage. Since a role for OPC in cancer prevention was postulated, we asked whether they have an effect on prostate cancer cells. METHODS: Cell proliferation was determined by (3)H-thymidine assay and cell cycle status was analyzed on a flow cytometer. Expression of regulators of proliferation and apoptosis was determined by Western blot. RESULTS: We found that androgen-responsive cells LNCaP are more sensitive to OPC in terms of inhibition of proliferation in comparison to androgen receptor-negative PC3 or DU145 cells. Treatment with OPC resulted in a decrease in the percentage of LNCaP cells in the S phase and an increase in the percentage of cells in sub G1 phase. The anti-proliferative and pro-apoptotic effect of OPC in the LNCaP cell line was associated with down-regulation of expression of the androgen receptor. Interestingly, similar regulatory effects of OPC, such as inhibition of expression of cyclin-dependent kinases and cyclins and stimulation of tumor suppressors p21 and p27, were seen in LNCaP and PC3 cells. Favorable changes in the Bcl-2/Bax ratio were observed in LNCaP and PC3 cells after the treatment with OPC. OPC caused an increase of phosphorylated mitogen-activated protein kinase p44 and p42, thus suggesting induction of cellular differentiation. CONCLUSIONS: We conclude that OPC is a candidate that fulfills criteria for chemopreventive strategies in prostate cancer that might be established in following in vivo studies.

Immunohistochemical evaluation of H-R3 a novel humanized monoclonal antibody that neutralizes the EGF-receptor.

The epidermal growth factor receptor (EGF-R) is an important growth regulator of epithelial cancer cells, overexpressed by several human tumors and scantly detectable in most normal tissues. The introduction of monoclonal antibodies (Mabs) and more recently engineered humanized Mabs have greatly expanded the therapeutic potential of this modality of cancer treatment. The present study was designed to compare the specificity of the murine and humanized anti-EGF-R Mabs. Biotinylated Mabs were tested in samples of fetal and adult normal and neoplastic tissues by ABC peroxidase method. All fetal tissues studied were positive for both Mabs, showing 2 different staining patterns, one homogeneous and finely granular in cytoplasm and another grosser with intense labeling in both membrane and cytoplasm. A similar recognition pattern was exhibited in adult normal tissues, where an intense reactivity was also evidenced in skin, tongue, gastrointestinal tract, renal tubules, and breast gland epithelium. In tissues from genitourinary and central nervous system, a faint staining was demonstrate, whereas those from cardiovascular and lymphoid tissues proved to be negative. These Mabs exhibited a heterogeneous and strong membrane and cytoplasm staining in neoplastic cells from lung, breast, and head and neck cancer. On the basis of these results, we conclude that the humanized (h-R3) and murine (egf/r3) anti-EGF-R Mabs show a very similar immunohistochemical pattern of recognition of fetal, adult, and neoplastic tissues. Also h-R3 Mab is a novel candidate for the development of an immunotherapeutic approach suitable for the treatment of tumors with EGF-R overexpression.

Benign breast lesions that simulate malignancy: magnetic resonance imaging with radiologic-pathologic correlation.

The typical appearance of benign breast conditions on magnetic resonance imaging (MRI) is well established and diagnosis is usually easy. However, cases of benign breast lesions that are extremely difficult to differentiate from malignant breast tumors are occasionally encountered in MRI of the breast because overlap between benign and malignant lesions characteristics is found. This article describes the MRI features of a variety of suspicious breast conditions that were confirmed to be benign in the histopathologic study. We evaluated both enhancement kinetics and lesion morphological information to differentiate malignant from benign lesions. We also correlated the MRI findings with clinical data, and mammographic, ultrasound, and pathologic findings. Lesions evaluated included benign proliferative breast disease, fibroadenoma, intraductal papilloma, granular cell tumor, pseudoangiomatous stromal hyperplasia, fat necrosis, mastitis, inflammatory granuloma, epidermal inclusion cyst, and benign intramammary lymph node.

Análisis evolutivo de la calidad de la solución final de diálisis en España y Portugal / Evolutional analysis of the quality of the final dialysis solution in Spain and Portugal

Las soluciones de diálisis contaminadas con aluminio representan la fuente de exposición al aluminio más peligrosa en pacientes en diálisis. El objetivo de este trabajo fue conocer la concentración de aluminio en la solución final de diálisis de los centros españoles y portugueses en el año 2004, y compara restos resultados con los obtenidos en estudios previos. En el presente estudio los centros españoles participantes fueron 248 y los portugueses 54. El aluminio pudo ser medido en todas las muestras recibidas. Estudios similares y realizados con la misma metodología fueron hechos en España en 1990, 1994 y 1999, y en Portugal en 1999 y 2001.El porcentaje de centros españoles con aluminio en la solución final de diálisis inferior a 2 µg/L se ha ido incrementando progresivamente desde el primer estudio en1990, hasta este último de 2004. En Portugal, el porcentaje de centros con aluminio en la solución final de diálisis inferior de 2 µg/L fue de 91,7% en 1999, 85,7% en 2001 y de 94,4% en 2004.En todos los estudios realizados en España el porcentaje de centros con niveles indetectables de aluminio (<1µg/L) aumentó; esta mejoría se observó hasta 1999, ya que en2004 el porcentaje se mantuvo estable. En Portugal dicho porcentaje se ha mantenido estable desde el año 1999 hasta la actualidad. El estudio realizado en 2004 en España y Portugal y su comparación con estudios similares previos, de muestran que la calidad de las soluciones de diálisis ha mejorado notablemente durante los últimos 15 años

Dialysis solutions contaminated with aluminium represent the most dangerous source of exposure to aluminium indialysis patients. The aim of this work was to determine the concentration of aluminium in the final dialysis solution in Spanish and Portuguese hospitals in 2004, and compare these results to those obtained in previous studies. In this study, the number of Spanish hospitals participating was 248 and number of Portuguese was 54. The aluminium could be measured in all the samples received. Similar studies using the same methodology were carried out in Spain in1990, 1994 and 1999, and in Portugal in 1999 and 2001. The percentage of Spanish centres with less than 2 µg/L of aluminium in the final dialysis solution has increased gradually since the first study in 1990, until this study in 2004.In Portugal, the percentage of hospitals with less than 2µg/L of aluminium in the final dialysis solution was 91.7% in 1999, 85.7% in 2001 and 94.4% in 2004.In all the studies carried out in Spain, the percentage of hospitals with undetectable levels of aluminium (≤ 1µg/L) increased; this improvement was observed up to 1999, since in2004 the percentage remained stable. In Portugal this percentage has remained stable since 1999 until the present. The study carried out in 2004 in Spain and Portugal and its comparison with previous similar studies shows that the quality of dialysis solutions has improved significantly over the last 15 years

Endogenous free polyamines and their role in fruit set of low and high parthenocarpic ability citrus cultivars.

Endogenous free polyamines (PAs), putrescine, spermidine and spermine, from developing fruitlets of Citrus species (Citrus unshiu Marc. and Citrus clementina Hort ex Tanaka) which differ in their parthenocarpic ability, and from uniflowered leafy and leafless inflorescences differing in their ability to set, have been determined by dansylation and separation of dansyl derivatives by HPLC. No significant differences in PAs content were observed between species or between leafy and leafless inflorescences which, nevertheless, significantly differed in fruit set. However, significant differences in their content were found in developing fruitlets, depending on the preceding flowering intensity of the tree and on the fruitlet load. These results suggest that, in Citrus, PAs may act as a nitrogen source rather than a regulator of fruit set.

[Variance of the quality of life one year after leaving the ICU and mechanic ventilation]. / Variación de la calidad de vida al año de alta del ingreso en UCI y ventilación mecánica.

The quality of life is a parameter used as a method to evaluate the social welfare result. It allows us to measure how entering in an ICU and mechanic ventilation (MV) influences the quality of life of patients in relation to their previous basal situation. To do so we have based ourselves on Barthel's functional scale; having the patient/family fill in a questionnaire on entrance to the ICU, one month later and a year after leaving it. The study is done on 135 patients who needed MV. A month after leaving the ICU 80 had survived, a year later we have only been able to interview on the phone 45 patients (4 exitus vs 41 alive), out if the remaining (35) patients we know from their clinical histories that 21 of them were alive one year later, only 3 exitus, and we do not have any further registers of the other 11 patients. The same as other studies have shown, the sick people who have a previous worse quality of life (Barthel < or = 75) are the ones who one month later have lost the most independence to carry out everyday activities (Barthel 45 33), although those who survive a year after have recovered the same level of autonomy they had previous to entering the ICU. Regarding the subjective evaluation of their stay in the unit, 18 patients (43%) have no memory of their stay in the unit, and out of the remaining 23, 17 have good memories and are satisfied with the treatment received by the staff.4 out of the questioned patients declared not wanting to enter the ICU, due to a subjective feeling of worsening in their quality of life (although they all had a Barthel > 70 which is equal to an independent quality of life).Also, a total of 22 patients take more medication than before entering the ICU: 2 1 medicines more per day.