Fermentative capabilities of native yeast strains grown on juices from different Agave species used for tequila and mezcal production.

The Asparagaceae family is endemic from America, being the Agave genus the most important. The Agave species possess economic relevance and are use as raw material to produce several distilled alcoholic beverages, as bacanora, tequila, and mezcal. The fermentation process has been carry out either spontaneously or by adding a selected yeast strain. The latter is generally responsible for the production of ethanol and volatile compounds. This study comprised five Agave species (A. angustifolia, A. cupreata, A. durangensis, A. salmiana, and A. tequilana) and eight endogenous yeast strains: five of them were non-Saccharomyces (Torulaspora delbrueckii, Zygosaccharomyces bisporus, Candida ethanolica, and two Kluyveromyces marxianus) and three Saccharomyces cerevisiae strains. The results showed that the S. cerevisiae strains were not able to grow on A. durangensis and A. salmiana juices. The Kluyveromyces marxianus strains grew and fermented all the agave juices and displayed high ethanol production (48-52 g L-1) and volatile compounds. The ethanol production was higher on A. angustifolia juice (1.1-2.8-fold), whereas the volatile compound was dependent on both yeast strain and the Agave species. The use of endogenous non-Saccharomyces yeast strains is feasible, as they may outperform S. cerevisiae regarding the production of fermented beverages from agave plants with a high content of ethanol and aromatic compounds. Graphical abstract.

The combined presence of CD20 + B cells and PD-L1 + tumor-infiltrating lymphocytes in inflammatory breast cancer is prognostic of improved patient outcome.

PURPOSE: The purpose of the study was to evaluate protein expression of PD-L1 and CD20 as prognostic biomarkers of patient outcome in inflammatory breast cancer (IBC) samples. METHODS: PD-L1 and CD20 protein expression was measured by immunohistochemistry in 221 pretreatment IBC biopsies. PD-L1 was assessed in tumor cells (PD-L1+ tumor cells) and tumor stromal infiltrating lymphocytes (PD-L1+ TILs); CD20 was scored in tumor-infiltrating B cells. Kaplan-Meier curves and Cox proportional hazard models were used for survival analysis. RESULTS: PD-L1+ tumor cells, PD-L1+ TILs, and CD20+ TILs were found in 8%, 66%, and 62% of IBC, respectively. PD-L1+ tumor cells strongly correlated with high TILs, pathological complete response (pCR), CD20+ TILs, but marginally with breast cancer-specific survival (BCSS, P = 0.057). PD-L1+ TILs strongly correlated with high TILs, CD20+ TILs, and longer disease-free survival (DFS) in all IBC and in triple-negative (TN) IBC (P < 0.035). IBC and TN IBC patients with tumors containing both CD20+ TILs and PD-L1+ TILs (CD20+TILs/PD-L1+TILs) showed longer DFS and improved BCSS (P < 0.002) than patients lacking both, or those with either CD20+ TILs or PD-L1+ TILs alone. In multivariate analyses, CD20+TILs/PD-L1+TILs status was an independent prognostic factor for DFS in IBC (hazard ratio (HR): 0.53, 95% CI 0.37-0.77) and TN IBC (HR: 0.39 95% CI 0.17-0.88), and for BCSS in IBC (HR: 0.60 95% CI 0.43-0.85) and TN IBC (HR: 0.38 95% CI 0.17-0.83). CONCLUSION: CD20+TILs/PD-L1+TILs status represents an independent favorable prognostic factor in IBC and TN IBC, suggesting a critical role for B cells in antitumor immune responses. Anti-PD-1/PD-L1 and B cell-activating immunotherapies should be explored in these settings.

High prevalence and risk factors associated with latent tuberculous infection in two Colombian prisons.

SETTING: Two prisons in Medellín and Itagüí, Colombia. OBJECTIVE: To determine the prevalence of tuberculin skin test (TST) positivity in prisoners and the annual risk of tuberculous infection (ARTI), to identify risk factors associated with a positive result, and to describe progression to active disease. DESIGN: Cross-sectional study. Inmates were included if time of incarceration was ⩾1 year and excluded if subjects had had previous or active tuberculosis (TB), or conditions that could hamper TST administration or interpretation. RESULTS: We screened 1014 inmates. The overall prevalence of TST positivity was 77.6%. The first TST administration resulted in 66% positivity, and the second TST an additional 11.6%. In Prison One, the ARTI was 5.09% in high TB incidence cell blocks and 2.72% in low TB incidence blocks. In Prison Two, the ARTI was 2.77%. Risk factors associated with TST positivity were history of previous incarceration and length of incarceration. Among all those included in the study, four individuals developed active pulmonary TB. CONCLUSION: Prevalence of TST positivity in prisoners and the ARTI were higher than in the general population, but differed between prisons; it is important to apply a second TST to avoid an overestimation of converters during follow-up.

Phase IB study of the combination of docetaxel, gemcitabine, and bevacizumab in patients with advanced or recurrent soft tissue sarcoma: the Axtell regimen.

BACKGROUND: To assess the response of patients with soft tissue sarcoma (STS) to the combination of docetaxel, bevacizumab, and gemcitabine. Vascular endothelial growth factor (VEGF)-A levels and expression of VEGF-A and VEGF receptors 1 and 2 were evaluated. PATIENTS AND METHODS: Thirty-eight chemotherapy-naive patients with STS were enrolled. A dose-finding study for gemcitabine from 1000, 1250, then 1500 mg/m(2) was done in nine patients (three cohorts), followed by an expansion cohort of 27 patients. Dose of docetaxel was 50 mg/m(2), bevacizumab was 5 mg/kg, and gemcitabine was 1500 mg/m(2), every 2 weeks. Serum VEGF-A was measured by enzyme-linked immunosorbent assay and tissue VEGF-A and its receptors by immunohistochemistry. RESULTS: The median follow-up was 36 months. The overall response rate observed was 31.4%, with 5 complete and 6 partial responses, and 18 stable diseases lasting for a median of 6 months. There was no significant hematologic toxicity. The adverse events with the highest grade were attributed to bevacizumab. There was no correlation of VEGF pathway biomarkers with outcome. CONCLUSIONS: The combination of gemcitabine, docetaxel, and bevacizumab is safe and effective in patients with STS. The most concerning adverse events were consequences of bevacizumab administration. The benefit of bevacizumab in this patient population remains unclear.

Epidermal growth factor receptor as a biomarker for cervical cancer.

This review focuses on the different modes of expression of the epidermal growth factor receptor (EGFR). All methods used to assess EGFR expression are critically analyzed and insights into the use of inhibitors of EGFR for treatment of cervical cancer are discussed. Currently, expression of EGFR as a biomarker for prognosis or for treatment of cervical cancer is not defined for clinical use.

Absence of epidermal growth factor receptor mutations in cervical cancer.

Epidermal growth factor receptor (EGFR) is overexpressed in the majority of cervical cancers (CCs). Somatic mutations of EGFR have been associated with clinical response to tyrosine kinase inhibitors (TKIs) in lung cancer patients. This study was designed to establish the frequency of EGFR point mutations in patients diagnosed with high-grade squamous intraepithelial lesions (HSIL) and CC. Nine cell lines derived from CC were screened for EGFR mutations in exons 18 through 21. Eighty-nine patient samples derived from invasive CC (n = 80) and HSIL (n = 9) were analyzed for the presence of EGFR mutations in exons 19 and 21. We found no mutations affecting the EGFR kinase domain in exons 18 through 21 in all cell lines tested, and no EGFR mutations were detected in exons 19 and 21 in all 89 human neoplastic samples analyzed. These data indicate that mutations in the EGFR kinase domain are very rare in CC and HSIL. Our results suggest, therefore, that treatment of CC patients with TKIs may not have the same efficacy as seen in patients with lung cancer, and that targeting the EGFR with other inhibitors may be more appropriate.

Protocolo de manejo de pancreatitis aguda. Hospital Universitario San Ignacio (HUSI) Bogotá / Acute Pancreatitis Protocol, Hospital Universitario San Ignacio (HUSI), Bogotá

La pancreatitis aguda es la inflamación aguda del páncreas con grado variable de compromiso de los tejidos regionales y diferente grado de compromiso sistémico. Se utilizan como definiciones las establecidas en el consenso de Atlanta (anexo 1). B. Diagnóstico 1. Historia clínica. Se presenta dolor en hemiabdomen superior, usualmente serio y acompañado de grados variables de vómito, náuseas y fiebre. Son importantes los antecedentes personales y familiares. 2. En el examen físico siempre se deben incluir el peso, la talla, el índice de masa corporal (IMC), la temperatura, la saturación de oxígeno (SAO2), la frecuencia cardiaca, la frecuencia respiratoria y la tensión arterial.

Malaria in a liver transplant recipient: a case report.

Malaria is an exotic complication in liver transplants patients. It can be acquired either by transfusion of blood products or through the transplanted organ. Infections caused by Plasmodium spp are unusual in liver transplants; to date, only four cases have been reported in the literature. Herein we have presented a case of Plasmodium vivax in a liver transplant patient. This diagnosis must be excluded in febrile transplant patients in endemic areas, especially during the first 2 months. An epidemiological history relevant for malaria both in the donor and in the recipient must be routinely included with screening tests.

Herniorrafia inguinal: diez años de seguimiento / Inguinal herniorraphy: ten years follow-up

La hernia inguinal constituye una de las patologias que con más frecuencia recibe tratamiento quirurgico a nivel mundial, y a pesar de ello no hay consenso universal en cuanto al tipo de cirugia ideal. Entre las principales medidas de calidad de la hemiorrafia se encuentran los indices de recurrencia, que en series personales o de centros especializados se ha reportado entre 1 y 2 por ciento, pero que no ha sido reproducible en centros docentes por cirujanos con diferente nivel de experiencia y en forma no estandarizada, donde se han reportado cifras hasta del 15 por ciento. En el siguiente trabajo, se presenta la experiencia de diez años con la cirugia de hernia inguinal por via anterior en el Hospital Universitario San Ignacio, cuyos resultados buscan establecer conductas futuras más efectivas en el manejo de estos pacientes. Se encontro una tasa inaceptablemente alta de recurrencia a largo plazo (16 por ciento) con el uso del reparo a la cintilla iliopubica, lo cual planteó la busqueda de alternativas quirurgicas mas seguras en los pacientes con hernias inguinales indirectas y orificio profundo debilitado, los cuales constituyen su principal indicacion. Asimismo, la baja morbilidad y mortalidad de la tecnica de McVAY, unidas a una recurrencia del 7 por ciento, la hacen una altemativa segura y eficaz. en el reparo de cualquier tipo de hernia inguinal no complicada por via anterior.

Albúmina y proteina C reactiva como predictores tempranos de falla orgánica múltiple en pacientes traumatizados / Serum albumin and C-reactive protein as early predictors of multiple organ system failure on trauma

La falla organica multiple (FOM) sigue siendo la principal causa de mortalidad tardia en el trauma, y los esfuerzos actuales estan encaminados a la deteccion de elementos que puedan predecir en forma temprana cuales pacientes van a desarrollar este sindrome, para incluirlos en protocolos de investigacion en los que se empleen medidas terapeuticas agresivas que puedan modificar su pronostico. En el presente estudio se identifican como factores de prediccion la albumina serica y la proteina C reactiva, dos parámetros de facil determinacion, de amplia disponibilidad en la mayoria de hospitales y de bajo costo, los cuales serán de utilidad en la estratificacion de los pacientes severamente traumatizados que requieren un cuidado crítico más agresivo.

Mapping the sites of putative tumor suppressor genes at 6p25 and 6p21.3 in cervical carcinoma: occurrence of allelic deletions in precancerous lesions.

Allelic deletions on the short arm of chromosome 6 (6p) are one of the common, possibly early, genetic changes that occur in the pathogenesis of cervical carcinoma (CC). Previous loss of heterozygosity (LOH) studies in CC identified a number of critical regions of deletions on 6p. However, the precise location of minimally deleted regions and their role in precancerous lesions have not been well characterized. To address these questions, we first performed a detailed LOH analysis on 6p in 59 cases of invasive CC. The pattern of LOH identified two minimal regions of deletions, one spanning a 5 cM genetic distance at 6p25 and a second site of 10.3 cM deletion mapping to 6p21.3. The 6p21.3 minimal deletion spans HLA class I genes. To understand the role of 6p genetic alterations in the development of CC, we also investigated 12 high-grade and 4 low-grade cases of cervical intraepithelial neoplasia (CIN) for LOH after laser microdissection. The high-grade CINs exhibited 91.7% LOH, and low-grade CINs had 50% LOH. These findings implicate the presence of at least two tumor suppressor genes on 6p relevant to CC and suggest that these genetic alterations occur very early in CC development. This study should therefore facilitate the identification of tumor suppressor genes on 6p and may identify which CINs are at high risk of progressing to invasive CC.

Identification of a 6-cM minimal deletion at 11q23.1-23.2 and exclusion of PPP2R1B gene as a deletion target in cervical cancer.

Previous functional and deletion mapping studies on cervical cancer (CC) have implicated one or more tumor suppressor genes (TSGs) on chromosome 11 at q13 and q22-24 regions. Of these, the 11q22-24 region exhibits frequent allelic deletions in a variety of solid tumor types, suggesting the presence of critical genes for tumor suppression in this region. However, the precise region of deletion on 11q is not clearly defined in CC. In an attempt to accurately map the deleted region, we performed an extensive loss of heterozygosity (LOH) mapping in 58 tumors using 25 polymorphic loci on both the short and long arms. The pattern of LOH identified three sites of deletions, two on 11p (p15.11-p15.3 and p12-13), and one on 11q (q23.1-q23.2). The 11q23.1-q23.2 exhibited highest frequency (60.6%) of deletions, suggesting that this could be the site of a candidate TSG in CC. The minimal deletion at 11q23.1-23.2 was restricted to a 6-cM region between 123.5 and 129.5 cM genetic distance on chromosome 11, identifying the site of a potential TSG important in the pathogenesis of CC. At least five known genes and 28 UniGene clusters were mapped to the present commonly deleted region. In addition, we have excluded a previously known TSG PPP2R1B at 11q23 as a deletion target in CC. The definition of the minimal deletion and the availability of expressed sequence resources should facilitate the identification of the candidate TSG.

Herniorrafia preperitoneal: experiencia en el Hospital Universitario San Ignacio / Preperitoneal repair of inguinal hernia. Experience at San Ignacio University Hospital, Bogotá

Se presenta la experiencia del Hospital Universitario de San Ignacio (HUSI) en reparos herniarios por via preperitoneal, con una morbilidad y recurrencia dentro de los rangos publicados en la literatura. Se analizan los resultados de la cirugia en casos de hernias incarceradas, crurales y reproducidas que hasta el momento constituyen las principales indicaciones del procedimiento, el cual se proyecta hacia el futuro como una tecnica util y segura que permite su empleo en casi todos los tipos de defectos herniarios.

Traqueostomía percutánea / Percutaneous tracheostomy

La traqueostomia es un procedimiento realizado por el cirujano general de manera habitual a pacientes criticamente enfermos, hospitalizados en la Unidad de Cuidado Intensivo. En el mundo se venia efectuando la tecnica abierta convencional pero, a partir de 1985, se desarrolla la tecnica de traqueostomia percutanea, la cual alcanzo gran popularidad en todo el mundo debido a sus costos más bajos, al menor tiempo quirurgico y a la menor tasa de complicaciones. En el Hospital Universitario de San Ignacio se empezó a aplicar esta tecnica desde 1998 y para ello se diseño un estudio prospectivo de dos fases: la primera incluyo 8 pacientes a los cuales se les realizó el procedimiento en salas de cirugia; y la segunda incluyo otros 8 pacientes a los cuales se les realizó la traqueostomia percutanea en la Unidad de Cuidado Intensivo. Pudimos comprobar que la traqueostomia percutanea es un procedimiento seguro, rápido y eficaz.

Sepsis por cateter / Catheter sepsis

Con el advenimiento de las tecnicas de nutricion parenteral se hizo necesario el uso de cateteres venosos centrales. En el presente articulo se describen algunas de las complicaciones asociadas a su uso, se hace enfasis en la fisiopatologia, el diagnostico y la prevencion de una de las más serias, cual es la sepsis por cateter. Se presenta la experiencia del grupo de soporte metabolico y nutricional del departamento de cirugia del Hospital Universitario de San Ignacio, con un índice de infeccion de 3.2 por ciento, que se considera muy ajustado a nuestro tipo de pacientes.

Enhancement of thymic recovery after cyclosporine by recombinant human growth hormone and insulin-like growth factor I.

Correlation of thymic changes with the development of CsA-associated syngeneic graft-versus-host disease (sGVHD) suggested that the development of tolerance depends on the prompt regeneration of the thymus after stopping CsA. Accordingly, we have tested recombinant human growth hormone (rhGH) and recombinant human insulin-like growth factor I (rhIGF-1) to determine if they accelerate reconstitution of the rat thymus after CsA-induced involution. After 14 days of CsA, the thymus has marked medullary involution but normally recovers fully in 6 weeks. In this study, LEW rats were injected with vehicle, rhGH, or rhIGF-1 for 21 days after stopping CsA and were examined. The vehicle-treated rats showed partial recovery with respect to Hassall's corpuscles, class II antigen expression, medullary size, medullary dendritic cells (DC), and T cell maturation. The mature thymocytes were predominantly CD8+ T cells. Both rhGH and rhIGF-1 induced significant thymic enlargement compared with the vehicle-treated rats. They also both significantly enhanced regeneration with respect to Hassall's corpuscles. The mature thymocyte population had significantly greater CD4+ cells. In addition, rhIGF-1 induced a significant improvement in the medullary size and medullary DC. While the medullae of a normal thymus are in intimate contact with cortical class II antigen, after CsA the cortex adjacent to the medulla is primarily class II antigen negative. RhGH significantly increased the class II antigen in the deep cortex while rhIGF-1 demonstrated a trend toward greater expression in this region (P = 0.06). We conclude that rhGH and rhIGF-1 accelerate thymic regeneration post-CsA. Further studies are now indicated to establish the potential for these factors to enhance the development of antigen-specific tolerance.

Prevention of syngeneic graft-versus-host disease by recovery of thymic microenvironment after cyclosporine.

Following a course of cyclosporine, syngeneic rat radiation chimeras consistently develop a GVHD-like syndrome. Correlation of the thymic immunopathology with conditions leading to syngeneic graft-versus-host disease (sGVHD) suggested the hypothesis that reconstitution of the normal thymic microenvironment after CsA is necessary for self-tolerance. When thymic regeneration is impaired, as in rats receiving previous mediastinal irradiation, then self-reactive effector cells are not regulated and proceed to damage the target tissues. Alternately, it could be argued that the observed thymic abnormalities are irrelevant to sGVHD. To test the primary hypothesis, post-CsA thymic reconstitution was prevented by total thymectomy in unirradiated rats. These rats consistently developed acute type sGVHD seen at 7 and 21 days post-CsA while rats from the CsA-treated sham thymectomy control group failed to develop sGVHD. Because thymectomy prior to CsA blocks sGVHD, most likely the peripheral effector cells in the post-CsA thymectomy group were derived from the CsA-altered thymus. The absence of sGVHD in the sham group indicates that the thymus led to active regulation of these cells after stopping CsA. If regeneration of the thymus restored only negative selection, then the sham thymectomy group should have also developed sGVHD. Flow cytometry and morphology of the spleen and lymph nodes demonstrated that the thymectomized rats, like CsA-treated radiation chimeras, experienced a significant delay in maturation of T cells following CsA. In contrast to the usual model in radiation chimeras, however, the post-CsA thymectomized rats did not convert to chronic type sGVHD. The importance of an abnormal thymus for this transition was confirmed in syngeneic radiation chimeras. Thymectomy after CsA in these rats also blocked the rapid transition to chronic sGVHD.

Lipoxygenase inhibitors suppress intracellular calcium rise induced by ionomycin in rat thymocytes.

The lipoxygenase (LO) inhibitors nordihydroguaiaretic acid (NDGA) and 15S-hydroxy-5,8,11,13-(Z,Z,Z,E)-eicosatetraenoic acid (15-HETE) have been found to suppress the rise in free cytoplasmic Ca2+ concentration [( Ca2+]i) induced by the Ca2+ ionophores ionomycin and A23187 in rat thymocytes. Bromophenacyl bromide (BPB), a phospholipase A2 (PLA2) inhibitor, produced a much weaker inhibitory effect, and indomethacin, a cyclo-oxygenase inhibitor, practically did not influence the [Ca2+]i response to ionomycin. These findings implicate the involvement of LO product(s) in the [Ca2+]i rise triggered by the Ca2+ ionophores. The contribution of the NDGA-sensitive component to the ionomycin-induced [Ca2+]i rise was significant in the ionomycin concentration range of 0.1 nM to 0.1 microM whereas at higher doses of the ionophore it gradually diminished. By contrast, the [Ca2+]i rise induced by exogenous arachidonic acid (AA) or melittin, a PLA2 activator, was not suppressed but potentiated by NDGA. Ionomycin and exogenous AA also elicited opposite changes in thymocyte cytoplasmic pH (pHi): the former elevated the pHi while the latter induced a pronounced acidification of the cytoplasm. This difference in the pHi responses may account for the different sensitivity of ionomycin- and AA-elicited [Ca2+]i signal to LO inhibitors.

Inhibitors of arachidonic acid metabolism eliminate the increase in cytosolic free calcium induced by the mitogen concanavalin A in rat thymocytes.

Using inhibitors of arachidonic acid (AA) metabolism, the possible involvement of AA products in the generation of [Ca2+]i and the pHi rise induced by the mitogen concanavalin A (Con A) in rat thymocytes has been studied. The lipoxygenase inhibitor nordihydroguaiaretic acid (NDGA, 10 microM) and the phospholipase A2 inhibitor bromophenacyl bromide (10 microM) eliminated the [Ca2+]i signal induced by Con A; the cyclooxygenase blocker indomethacin also inhibited it. However, neither NDGA nor indomethacin suppressed the pHi rise stimulated by Con A. Exogenous AA induced an increase in [Ca2+]i but not in the pHi. These results indicate that AA metabolites, probably of the lipoxygenase pathway, take part in the generation of the [Ca2+]i response to the mitogen. In contrast, they appear not to be involved in the pHi rise evoked by Con A.