Mechanical properties of friction induced nanocrystalline pearlitic steel.

Nanocrystalline structured variants of commercially available alloys have shown potential for boosting the mechanical properties of these materials, leading to a reduction in waste and thereby retaining feasible supply chains. One approach towards achieving these nanostructures resides in frictional treatments on manufactured parts, leading to differential refinement of the surface structure as compared to the bulk material. In this work the machining method is considered to be a testing platform for the formation and study of frictional nanostructured steel, assembly of which is stabilized by fast cooling of the produced chip. Analysis of the mechanical properties has shown extraordinary results at the surface, over 2000 MPa of strength on AISI1045 steel, more than three times the strength of the base material, demonstrating at the same time a reduction of 15% in the elastic modulus. The microscopic analysis suggests a reassembly of the elements in a new lattice of carbon supersaturated nano-ferrite.

3+4 = 6? Implications of the stratification of localised Gleason 7 prostate cancer by number and percentage of positive biopsy cores in selecting patients for active surveillance. / ¿3 + 4 = 6? Implicaciones de la estratificación del cáncer de próstata localizado Gleason 7 por número y porcentaje de cilindros positivos de biopsia en la selección de pacientes para vigilancia activa.

OBJECTIVE: To determine whether the number and percentage of positive biopsy cores identify a Gleason 3+4 prostate cancer (PC) subgroup of similar biologic behaviour to Gleason 3+3. MATERIAL AND METHOD: An observational post-radical prostatectomy study was conducted of a cohort of 799 patients with localised low-risk (n=582, Gleason 6, PSA <10ng/ml and cT1c-2a) and favourable intermediate PC (n=217, Gleason 3+4, PSA ≤10 ng/ml and pT2abc). The Gleason 3+4 tumours were stratified by number (≤3 vs.>3) and by percentage of positive cores (≤33% vs. >33%). We analysed the tumours' association with the biochemical recurrence risk (BRR) and cancer-specific mortality (CSM). We conducted various predictive models using Cox regression and estimated (C-index) and compared their predictive capacity. RESULTS: With a median follow-up of 71 months, the BRR and CSM of the patient group with Gleason 3+4 tumours and a low number (≤3) and percentage (≤33%) of positive cores were not significantly different from those of the patients with Gleason 6 tumours. At 5 and 10 years, there were no significant differences in the number of biochemical recurrences, the probability of remaining free of biochemical recurrences, the number of deaths by PC or the probability of death by PC between the 2 groups. In contrast, the patients with Gleason 3+4 tumours and more than 33% of positive cores presented more deaths by PC than the patients with Gleason 6 tumours. At 10 years, the probability of CSM was significantly greater. This subgroup of tumours showed a significantly greater BRR (RR, 1.6; P=.02) and CSM (RR, 5.8, P≤.01) compared with the Gleason 6 tumours. The model with Gleason 3+4 stratified by the percentage of positive cores significantly improved the predictive capacity of BRR and CSM. CONCLUSIONS: Fewer than 3 cores and a percentage <33% of positive cores identifies a subgroup of Gleason 3+4 tumours with biological behaviour similar to Gleason 6 tumours. At 10 years, there were no differences in BRR and CSM between the 2 groups. These results provide evidence supporting active surveillance as an alternative for Gleason 3+4 tumours and low tumour extension in biopsy.

Telomere dysfunction and chromosome structure modulate the contribution of individual chromosomes in abnormal nuclear morphologies.

The cytokinesis-block micronucleus assay has emerged as a biomarker of chromosome damage relevant to cancer. Although it was initially developed to measure micronuclei, it is also useful for measuring nucleoplasmic bridges and nuclear buds. Abnormal nuclear morphologies are frequently observed in malignant tissues and short-term tumour cell cultures. Changes in chromosome structure and number resulting from chromosome instability are important factors in oncogenesis. Telomeres have become key players in the initiation of chromosome instability related to carcinogenesis by means of breakage-fusion-bridge cycles. To better understand the connection between telomere dysfunction and the appearance of abnormal nuclear morphologies, we have characterised the presence of micronuclei, nucleoplasmic bridges and nuclear buds in human mammary primary epithelial cells. These cells can proliferate beyond the Hayflick limit by spontaneously losing expression of the p16(INK4a) protein. Progressive telomere shortening leads to the loss of the capping function, and the appearance of end-to-end chromosome fusions that can enter into breakage-fusion-bridge cycles generating massive chromosomal instability. In human mammary epithelial cells, different types of abnormal nuclear morphologies were observed, however only nucleoplasmatic bridges and buds increased significantly with population doublings. Fluorescent in situ hybridisation using centromeric and painting specific probes for chromosomes with eroded telomeres has revealed that these chromosomes are preferentially included in the different types of abnormal nuclear morphologies observed, thus reflecting their common origin. Accordingly, real-time imaging of cell divisions enabled us to determine that anaphase bridge resolution was mainly through chromatin breakage and the formation of symmetric buds in daughter nuclei. Few micronuclei emerged in this cell system thus validating the scoring of nucleoplasmic bridges and nuclear buds for measuring chromosome instability in telomere-dysfunction cell environments.

The number of dysfunctional telomeres in a cell: one amplifies; more than one translocate.

Chromosomal instability is increasingly appreciated as a key component of tumorigenesis in humans. A combination of abnormal telomere shortening and cell-cycle checkpoint deficiency has been proposed as the initial lesions causing destabilizing chromatin bridges in proliferative cells. We examined the participation of the different types of end-to-end fusions in generating instable karyotypes in non-transformed human breast epithelial cells. We concluded that short dysfunctional telomeres represent an initiating substrate for post-replicative rejoining of sister chromatids and are likely to make an important contribution to the formation of chromosomal rearrangements and the amplification of chromosome arm segments in breast epithelial cells. We propose that there is a chronological order in the participation of the different types of end-to-end fusions in the generation of chromosomal instability. Thus, intrachromosomal post-replicative joining would proceed mainly in the early stages after overcoming growth arrest, when telomere dysfunction is limited and affects only one chromosome end in a cell. The absence of a second substrate for end joining will conduct the cell with the uncapped chromosome to replicate its DNA and fuse the uncapped sister chromatids after replication. Later, since telomeres shorten progressively with each DNA replication round, the uncapping will affect many more chromosome ends, and fusions between the uncapped ends from different chromosomes will be produced. While the fusion of sister chromatids will produce chromosome segment amplification and terminal deletions in the daughter cells, interchromosomal fusion will produce unbalanced rearrangements other than chromosome segment amplifications.

Utilización de medicamentos en adulto mayor: Hospital General Docente Agostinho Neto, 2006 / Use of drugs in older adult: General Teoching Hospital Agosthino Neto, 2006

La población geriátrica constituye un grupo muy importante de pacientes y más en estos momentos en que el mundo está envejeciendo rápidamente, actualmente 2500 000 de personas tienen mas de 65 años de edad y para el 2008 se espera que sean 69 000 000. En los países desarrollados, más del 20por ciento de la población será de la 3ra edad como consecuencia de un aumento de la esperanza de vida y la disminución de la natalidad. En nuestro país el comportamiento es similar al de países desarrollados por lo que debemos contribuir a mejorar la calidad de vida en este grupo poblacional, más sensible a los efectos adversos a los fármacos y la polimedicación en muchos casos justificada por las patologías crónicas que tienen asociadas. Método: Se realizó un estudio de utilización de medicamentos en el adulto mayor en los servicios de medicina del Hospital General de Docente de Guantánamo en el período Enero a Diciembre 2006 con el objetivo de identificar los grupos de medicamentos más utilizados, las patologías más frecuentemente asociadas y las reacciones adversas e interacciones medicamentosas de aparición más frecuente en el adulto mayor.Resultados: Los adultos mayores tienen asociados varios medicamentos por tener más de una patología asociada y en un importante por ciento de ellos han presentado RAM e Interacciones medicamentosas no siendo recogidas en las historias clínicas. Según distribución por edad y sexo se encontró que el 59por ciento de los adultos mayores tiene entre 70 y 74 años de edad, predominando el sexo femenino, el 100por ciento de los pacientes del estudio presentaron patologías crónicas asociadas, las de más frecuente aparición fue la hipertensión arterial (72,1por ciento), así como se apreció que el grupo farmacológico de mayor utilización fue el de los antihipertensivos (87,2 por ciento), seguido por los AINEs, los antiarrítmicos y los antibióticos de amplio espectro. En ningún caso se empleó la monoterapia, el 100por ciento de los pacientes tenían más de 2 fármacos y el 63,2 por ciento más de 3 fármacos. La reacción adversa que más predominó fue la cefalea (65,2 por ciento). Conclusiones: Se demuestra que el adulto mayor es polimedicado por lo que se recomienda el análisis de las normas de tratamiento para pacientes de la tercera edad que garantice una terapéutica adecuada con un menor número de fármacos.

Teratoma quístico maduro de tiroides: a propósito de un caso / Mature cystic teratoma of thyroid: a purpose of a case

Los Teratomas son tumores que están compuestos de tejidos derivados de las tres capas germinales. La localización más común en los niños son las sacrococcígeas (40 por ciento), mientras que los ubicados en cabeza y cuello, solo representan el 3,5 por ciento. Desde el punto de vista clínico, los pacientes consultan por la presencia de una masa en el cuello. Los estudios incluyen radiografía simple, ultrasonido, scan de la glándula tiroides, medición de AFP y ß-HCG. La extirpación quirúrgica es el tratamiento de elección. El presente caso clínico trata de un lactante mayor masculino de 12 meses de edad, quien presenta desde el nacimiento, aumento de volumen en la cara antero-lateral izquierda del cuello. Se solicita ecograma cervical reportando: Tumoración ecomixta latero cervical izquierda y ganmagrama tiroideo evidenciándose: bocio multinodular. A los 7 meses de edad se aprecia un aumento mayor de la tumoración y se indica nuevo ecograma: Lóbulo tiroideo izquierdo de tamaño aumentado, con gran imagen nodular, ecomixta. Por lo que se indica Cintilograma tiroideo con I131: Glándula deformada, con una zona hipocaptante que se relaciona con nódulo tiroideo. Se realiza Tiroidectomía ezquierda total con istmectomía. Encontrando hallazgos compatibles con TERATOMA QUÍSTICO MADURO. Los Teratomas de tiroides son tumores muy raros. La mayor incidencia se aprecia en recién nacidos hasta los 2 años de edad. Los pacientes con diagnóstico de malignidad, son tratados con quimioterapia, radioterapia o ambos. Actualmente el niño tiene 10 meses de haber sido intervenido y se encuentra clínicamente estable y sin recidivas.

[Usefulness of bcl-2 expression as a new basal cell marker in prostatic pathology]. / Utilidad de bcl-2 como nuevo marcador de expresión de células basales en patología prostática.

INTRODUCTION AND OBJECTIVES: The diagnosis of invasive adenocarcinoma of the prostate is often difficult in needle prostatic cores, where, additionally, the assessment of the presence of basal cells has demonstrated to be of paramount importance. Currently, the immunohistochemical expression of 34betaE12 antigen and p63 protein are the most utilized markers. In our study, we analyzed comparatively the expression of 34betaE12, p63, bcl-2 and alpha-methylacyl-CoA racemase in order to evaluate the usefulness of bcl-2 as a new marker of the basal cells in prostatic pathology. METHODS AND RESULTS: This study comprises radical prostatectomy specimens from 48 patients which were studied in order to determine the lack of staining of basal cells in invasive tumor areas together with the expression of racemase. Likewise, the presence of basal cells in areas of atrophy, hyperplasia, adenosis, and high-grade prostatic intraepithelial neoplasia (PIN) was also examined. Within the areas of adenosis and PIN a discontinuous pattern of basal cell expression was found in some cases. In 2 out of 48 cases (4,2%) of invasive carcinoma a weak bcl-2 expression without a basal cell distribution was found. Moreover, the expression of bcl-2 in the stromal lymphocytes appeared to be essential as an internal positive control of the technique. CONCLUSIONS: In addition to classical markers, we demonstrated the diagnostic value of bcl-2 as a new basal cell marker.

La historia clínica: documento médico legal sine qua non en la urgencia / Clinical history: A sine qua non legal medical document at urgency

Los frecuentes hechos de orden médico legal a que los médicos se enfrentan en la emergencia y que deben resolverse sin dilación en previsión de los posibles prejuicios que acarrean al paciente, la familia y al propio profesional, son múltiples. Cabe mencionar que la presión de la urgencia puede llevar a olvidar o relativizar la importancia de estos hechos de orden médico legal. La historia clínica constituye un documento médico de singular importancia en la práctica asistencial, este documento refleja las características de la relación médico-paciente a través del tiempo

Casos de solicitud de intervención policial en guardia / Cases of request of police intervention in guard

Información sobre los aspectos legales de diferentes situaciones que se plantean en la sala de guardia: fallecimientos, rechazos de internación y/o tratamiento, accidentes, y lesiones, entre otras

Unique subpopulations of CD56+ NK and NK-T peripheral blood lymphocytes identified by chemokine receptor expression repertoire.

CD56, an adhesion molecule closely related to neural cell adhesion molecule, is an immunophenotypic marker for several unique populations of PBLS: Although CD56(+) cells derive from multiple lymphocyte lineages, they share a role in immunosurveillance and antitumor responses. We have studied the chemokine receptor expression patterns and functional migratory responses of three distinct CD56(+) populations from human peripheral blood. NK-T cells were found to differ greatly from NK cells, and CD16(+) NK cells from CD16(-) NK cells. CD16(+) NK cells were the predominant population responding to IL-8 and fractalkine, whereas NK-T cells were the predominant population responding to the CCR5 ligand macrophage-inflammatory protein-1beta. CD16(-) NK cells were the only CD56(+) population that uniformly expressed trafficking molecules necessary for homing into secondary lymphoid organs through high endothelial venule. These findings describe a diverse population of cells that may have trafficking patterns entirely different from each other, and from other lymphocyte types.

Expression cloning of the STRL33/BONZO/TYMSTRligand reveals elements of CC, CXC, and CX3C chemokines.

STRL33/BONZO/TYMSTR is an orphan chemokine and HIV/SIV coreceptor receptor that is expressed on activated T lymphocytes. We describe an expression cloning strategy whereby we isolated a novel chemokine, which we name CXCL16. CXCL16 is an alpha (CXC) chemokine but also has characteristics of CC chemokines and a structure similar to fractalkine (neurotactin) in having a transmembrane region and a chemokine domain suspended by a mucin-like stalk. A recombinant version of CXCL16 fails to mediate chemotaxis to all known chemokine receptor transfectants tested but does mediate robust chemotaxis, high affinity binding, and calcium mobilization to Bonzo receptor transfectants, indicating that this is a unique receptor ligand interaction. In vitro polarized T cell subsets including Th1, Th2, and Tr1 cells express functional Bonzo, suggesting expression of this receptor in chronic inflammation, which we further verified by demonstration of CXCL16-mediated migration of tonsil-derived CD4(+) T lymphocytes. CXCL16 is expressed on the surface of APCs including subsets of CD19(+) B cells and CD14(+) monocyte/macrophages, and functional CXCL16 is also shed from macrophages. The combination of unique structural features of both Bonzo and CXCL16 suggest that this interaction may represent a new class of ligands for this receptor family. Additionally, this chemokine might play a unique dual role of attracting activated lymphocyte subsets during inflammation as well as facilitating immune responses via cell-cell contact.

CCR7 expression and memory T cell diversity in humans.

CCR7, along with L-selectin and LFA-1, mediates homing of T cells to secondary lymphoid organs via high endothelial venules (HEV). CCR7 has also been implicated in microenvironmental positioning of lymphocytes within secondary lymphoid organs and in return of lymphocytes and dendritic cells to the lymph after passage through nonlymphoid tissues. We have generated mAbs to human CCR7, whose specificities correlate with functional migration of lymphocyte subsets to known CCR7 ligands. We find that CCR7 is expressed on the vast majority of peripheral blood T cells, including most cells that express adhesion molecules (cutaneous lymphocyte Ag alpha(4)beta(7) integrin) required for homing to nonlymphoid tissues. A subset of CD27(neg) memory CD4 T cells from human peripheral blood is greatly enriched in the CCR7(neg) population, as well as L-selectin(neg) cells, suggesting that these cells are incapable of homing to secondary lymphoid organs. Accordingly, CD27(neg) T cells are rare within tonsil, a representative secondary lymphoid organ. All resting T cells within secondary lymphoid organs express high levels of CCR7, but many activated cells lack CCR7. CCR7 loss in activated CD4 cells accompanies CXC chemokine receptor (CXCR)5 gain, suggesting that the reciprocal expression of these two receptors may contribute to differential positioning of resting vs activated cells within the organ. Lymphocytes isolated from nonlymphoid tissues (such as skin, lung, or intestine) contain many CD27(neg) cells lacking CCR7. The ratio of CD27(neg)/CCR7(neg) cells to CD27(pos)/CCR7(pos) cells varies from tissue to tissue, and may correlate with the number of cells actively engaged in Ag recognition within a given tissue.

A novel chemokine ligand for CCR10 and CCR3 expressed by epithelial cells in mucosal tissues.

Mucosae-associated epithelial chemokine (MEC) is a novel chemokine whose mRNA is most abundant in salivary gland, with strong expression in other mucosal sites, including colon, trachea, and mammary gland. MEC is constitutively expressed by epithelial cells; MEC mRNA is detected in cultured bronchial and mammary gland epithelial cell lines and in epithelia isolated from salivary gland and colon using laser capture microdissection, but not in the endothelial, hemolymphoid, or fibroblastic cell lines tested. Although MEC is poorly expressed in skin, its closest homologue is the keratinocyte-expressed cutaneous T cell-attracting chemokine (CTACK; CCL27), and MEC supports chemotaxis of transfected lymphoid cells expressing CCR10, a known CTACK receptor. In contrast to CTACK, however, MEC also supports migration through CCR3. Consistent with this, MEC attracts eosinophils in addition to memory lymphocyte subsets. These results suggest an important role for MEC in the physiology of extracutaneous epithelial tissues, including diverse mucosal organs.

Developmental switches in chemokine response profiles during B cell differentiation and maturation.

Developing B cells undergo dramatic changes in their responses to chemoattractant cytokines (chemokines) and in expression of chemokine receptors. Bone marrow pre-pro-B cells (AA4.1(+)/natural killer 1.1(-) Fraction A cells) and cells capable of generating pro-B colonies in the presence of interleukin 7 and flt3 ligand migrate to thymus-expressed chemokine (TECK), a response lost in later stages of B cell development. B cell-attracting chemokine 1 (BCA-1) responses correlate with CXC chemokine receptor (CXCR)5 expression, are first displayed by a pro-B cell subset, are lost in pre-B cells, and then are regained just before and after egress from the marrow. All peripheral B cell subsets, including follicular and germinal center as well as marginal zone and peritoneal B1 B cells, respond to BCA-1, implying that responsiveness to this follicular chemokine is not sufficient to predict follicle localization. Responses to the CC chemokine receptor (CCR)7 ligands secondary lymphoid tissue chemoattractant (SLC) and macrophage inflammatory protein (MIP)-3beta, implicated in homing to lymphoid tissues, are upregulated before B cell exit from the marrow, but increase further in the periphery and are shared by all peripheral B cells. In contrast, responsiveness to MIP-3alpha and expression of CCR6 are acquired only after emigration to the periphery and during maturation into the recirculating B cell pool. Chemotaxis to stromal cell-derived factor 1alpha is observed at all stages of B cell differentiation. Thus, unique patterns of chemokine responses may help define developing B cell populations and direct their maturation in the marrow and migration to the periphery.

Amino-terminally modified RANTES analogues demonstrate differential effects on RANTES receptors.

Modification of the amino terminus of regulated on activated normal T-cell expressed (RANTES) has been shown to have a significant effect on biological activity and produces proteins with antagonist properties. Two amino-terminally modified RANTES proteins, Met-RANTES and aminooxypentane-RANTES (AOP-RANTES), exhibit differential inhibitory properties on both monocyte and eosinophil chemotaxis. We have investigated their binding properties as well as their ability to activate the RANTES receptors CCR1, CCR3, and CCR5 in cell lines overexpressing these receptors. We show that Met-RANTES has weak activity in eliciting a calcium response in Chinese hamster ovary cells expressing CCR1, CCR3, and CCR5, whereas AOP-RANTES has full agonist activity on CCR5 but is less effective on CCR3 and CCR1. Their ability to induce chemotaxis of the murine pre-B lymphoma cell line, L1.2, transfected with the same receptors, consolidates these results. Monocytes have detectable mRNA for CCR1, CCR2, CCR3, CCR4, and CCR5, and they respond to the ligands for these receptors in chemotaxis but not always in calcium mobilization. AOP-RANTES does not induce calcium mobilization in circulating monocytes but is able to do so as these cells acquire the macrophage phenotype, which coincides with a concomitant up-regulation of CCR5. We have also tested the ability of both modified proteins to induce chemotaxis of freshly isolated monocytes and eosinophils. Cells from most donors do not respond, but occasionally cells from a particular donor do respond, particularly to AOP-RANTES. We therefore hypothesize that the occasional activity of AOP-RANTES to induce leukocyte chemotaxis is due to donor to donor variation of receptor expression.

[Multiple analysis of morphologic factors with prognostic value in transitional cell papillary carcinoma of the bladder. Retrospective study of 571 cases]. / Análisis múltiple de factores morfológicos con valor pronóstico en el carcinoma papilar de células transicionales de vejiga. Un estudio retrospectivo de 571 casos.

A 7-year retrospective study of 571 cases of transitional cell carcinoma of the bladder (1990-1996) was made in order to demonstrate, statistically, the existence of a close relation between the tumoral staging of Jewett and the cytological grading of Mostofi (p < 0.05). From the results obtained we deduce that grades 1 and 2 are usually associated with stage A tumours, whereas grade 3 is associated with stage B. Thereafter all stage B tumours (184 cases) were selected to determine whether or not cytological grading was related to any histological parameter in order to differentiate between superficial (stage B1) and deeply invasive tumours (stage B2). According to results obtained, the existence of a close relation between grading and the way of muscular infiltration in a focal or diffuse manner could be suggested. These data will be correlated to prognosis in a subsequent clinical follow-up. Therefore, we conclude that grades 1 and 2 usually infiltrate the muscular layer of the bladder in a focal manner with better prognosis, while grade 3 tumors infiltrate in a diffuse way with a poor prognosis.