Multi-institutional competing risks analysis of distant brain failure and salvage patterns after upfront radiosurgery without whole brain radiotherapy for brain metastasis.

Background: In this study, we use a competing risks analysis to assess factors predictive of early-salvage whole brain radiotherapy (WBRT) and early death after upfront stereotactic radiosurgery (SRS) alone for brain metastases in an attempt to identify populations that benefit less from upfront SRS. Patients and methods: Patients from eight academic centers were treated with SRS for brain metastasis. Competing risks analysis was carried out for distant brain failure (DBF) versus death prior to DBF as well as for salvage SRS versus salvage WBRT versus death prior to salvage. Linear regression was used to determine predictors of the number of brain metastases at initial DBF (nDBF). Results: A total of 2657 patients were treated with upfront SRS alone. Multivariate analysis (MVA) identified an increased hazard of DBF associated with increasing number of brain metastases (P < 0.001), lowest SRS dose received (P < 0.001), and melanoma histology (P < 0.001), while there was a decreased hazard of DBF associated with increasing age (P < 0.001), KPS < 70 (P < 0.001), and progressive systemic disease (P = 0.004). MVA for first salvage SRS versus WBRT versus death prior to salvage revealed an increased hazard of first salvage WBRT seen with increasing number of brain metastases (P < 0.001) and a decreased hazard with widespread systemic disease (P = 0.002) and increasing age (P < 0.001). Variables associated with nDBF included age (P = 0.02), systemic disease status (P = 0.03), melanoma histology (P = 0.05), and initial number of brain metastases (P < 0.001). Conclusions: Patients with a higher initial number of brain metastases were more likely to experience DBF, have a higher nDBF, and receive early-salvage WBRT, while patients who were older, had lower KPS, or had more systemic disease were more likely to experience death prior to DBF or salvage WBRT.

Discrepancies between biomarkers of primary breast cancer and subsequent brain metastases: an international multicenter study.

PURPOSE: Discordances between the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), expression between primary breast tumors and their subsequent brain metastases (BM) were investigated in breast cancer patients. METHODS: We collected retrospective data from 11 institutions in 8 countries in a predefined-standardized format. Receptor status (positive or negative) was determined according to institutional guidelines (immunohistochemically and/or fluorescence in situ hybridization). The study was subject to each institution's ethical research committee. RESULTS: A total of 167 breast cancer patients with BM were included. 25 patients out of 129 with a complete receptor information from both primary tumor and BM (ER, PR, HER2) available, had a change in receptor status: 7 of 26 (27%) ER/PR-positive/HER2-negative primaries (3 gained HER2; 4 lost expression of ER/PR); 10 of 31 (32%) ER/PR-positive/HER2-positive primaries (4 lost ER/PR only; 3 lost HER2 only; 3 lost both ER/PR and HER2); one of 33 (3%) ER/PR-negative receptor/HER2-positive primaries (gained ER); and 7 of 39 (18%) triple-negative primaries (5 gained ER/PR and 2 gained HER2). CONCLUSIONS: The majority of breast cancer patients with BM in this series had primary HER2-enriched tumors, followed by those with a triple-negative profile. One out of 5 patients had a receptor discrepancy between the primary tumor and subsequent BM. Therefore, we advise receptor status assessment of BM in all breast cancer patients with available histology as it may have significant implications for therapy.

A comprehensive review of MR imaging changes following radiosurgery to 500 brain metastases.

BACKGROUND AND PURPOSE: Stereotactic radiosurgery is known to control 85%-95% of intracranial metastatic lesions during a median survival of 6-8 months. However, with the advent of newer systemic cancer therapies, survival is improving; this change mandates a longitudinal quantitative analysis of the radiographic response of brain metastases to radiosurgery. MATERIALS AND METHODS: MR imaging of 516 metastases in 120 patients treated with GK-SRS from June 2006 to December 2009 was retrospectively reviewed. Lesion volume at initial treatment and each follow-up was calculated by using the following formula: length × width × height / 2. Volume changes were correlated with patient demographics, histopathology, and radiation treatment variables. RESULTS: Thirty-two percent of lesions increased in volume following radiosurgery. Clinically, this translated into 54% of patients having ≥1 of their lesions increase in size. This increase begins at 6 weeks and can last beyond 15 months' post-SRS. Male sex (P = .002), mean voxel dose <37 Gy (P = .009), and initial treatment volume >500 mm(3) (P < .001) are associated with posttreatment increases in tumor size. Median survival following radiosurgery was 9.5 months for patients with all lesions exhibiting stable/decreased volumes, >18.4 months for patients with all lesions exhibiting increased volumes, and 16.4 months for patients with mixed lesional responses. CONCLUSIONS: Most metastatic lesions are stable or smaller in size during the first 36 months post-SRS. However, a transient increase in volume is seen in approximately one-third of lesions. Sex, treatment dose, initial lesion size, and histopathology all correlate with variations in lesion volume post-SRS. The longer the patient survives, the more likely an increase in lesion size will be seen on follow-up imaging.

Nefroma mesoblástico infantil: informe de un caso clínico y revisión bibliográfica / Mesoblastic nephroma in children: report of a clinic case and bibliographic revision

En una paciente pediátrica de 2 meses y medio se detecta por ecografía un tumor en el polo superior del riñón derecho, que debutó clínicamente por hematuria. Los exámenes de ingreso demostraron buen estado general, ausencia de masa abdominal palpable, y exámenes de laboratorio normales. La TAC abdominal confirma una masa de 3,1x 2,5cm., sin invasión aparente de la grasa perirrenal.Se somete a laparotomía exploradora que demuestra un tumor renal derecho que ocupa un 80 por ciento de éste órgano, sin compromiso ganglionar hiliar ni paraaórtico, en tanto que el riñon izquierdo está indemne.El estudio histológico concluyó que se trata de un nefroma mesoblástico, tumor infrecuente y que debe diferenciarse rigurosamente del tumor de Wilms, pues su pronóstico casi siempre es muy bueno sólo con cirugía. Se describe la lesión y los métodos aplicados para el diagnóstico diferencial. Los autores revisan la literatura disponible de estas lesiones, raras en la práctica clínica habitual

Ventriculopleural shunt obstruction and positive-pressure ventilation. Case report.

The authors report an unusual case of a patient with low-pressure hydrocephalus and a ventriculopleural shunt, in whom routine respiratory management performed using positive-pressure ventilation caused shunt obstruction and coma. While the patient received positive-pressure ventilation with external cerebrospinal fluid (CSF) drainage at subatmospheric pressure, the ventricles returned to normal size and the coma rapidly reversed. After the authors' recognition of the effect of positive-pressure ventilation on intrapleural pressure and ventriculopleural shunt function, and the subsequent removal of positive-pressure ventilation, CSF flow through the shunt resumed and the patient's coma resolved.

cDNA cloning, chromosomal localization, and expression analysis of human BEHAB/brevican, a brain specific proteoglycan regulated during cortical development and in glioma.

BEHAB (Brain Enriched HyAluronan Binding)/brevican, a brain-specific member of the lectican family of chondroitin sulfate proteoglycans (CSPGs), may play a role in both brain development and human glioma. BEHAB/brevican has been cloned from bovine, mouse and rat. Two isoforms have been reported: a full-length isoform that is secreted into the extracellular matrix (ECM) and a shorter isoform with a sequence that predicts a glycophosphatidylinositol (GPI) anchor. Here, we report the characterization of BEHAB/brevican isoforms in human brain. First, BEHAB/brevican maps to human chromosome 1q31. Second, we report the sequence of both isoforms of human BEHAB/brevican. The deduced protein sequence of full-length, secreted human BEHAB/brevican is 89.7, 83.3 and 83.2% identical to bovine, mouse and rat homologues, respectively. Third, by RNase protection analysis (RPA) we show the developmental regulation of BEHAB/brevican isoforms in normal human cortex. The secreted isoform is highly expressed from birth through 8years of age and is downregulated by 20years of age to low levels that are maintained in the normal adult cortex. The GPI isoform is expressed at uniformly low levels throughout development. Fourth, we confirm and extend previous studies from our laboratory, here demonstrating the upregulation of BEHAB/brevican mRNA in human glioma quantitatively. RPA analysis shows that both isoforms are upregulated in glioma, showing an approximately sevenfold increase in expression over normal levels. In contrast to the developmental regulation of BEHAB/brevican, where only the secreted isoform is regulated, both isoforms are increased in parallel in human glioma. The distinct patterns of regulation of expression of the two isoforms suggest distinct mechanisms of regulation of BEHAB/brevican during development and in glioma.

A xylem-specific cellulose synthase gene from aspen (Populus tremuloides) is responsive to mechanical stress.

Angiosperm trees accumulate an elevated amount of highly crystalline cellulose with a concomitant decrease in lignin in the cell walls of tension-stressed tissues. To investigate the molecular basis of this tree stress response, we cloned a full-length cellulose synthase (PtCesA) cDNA from developing xylem of aspen (Populus tremuloides). About 90% sequence similarity was found between the predicted PtCesA and cotton GhCesA proteins. Northern blot and in situ hybridization analyses of PtCesA gene transcripts in various aspen tissues, and PtCesA gene promoter-beta-glucuronidase (GUS) fusion analysis in transgenic tobacco, demonstrated conclusively that PtCesA expression is confined to developing xylem cells during normal plant growth. During mechanical stress induced by stem bending, GUS expression remained in xylem and was induced in developing phloem fibers undergoing tension stress, but was turned off in tissues undergoing compression on the opposite side of the bend. Our results suggest a unique role for PtCesA in cellulose biosynthesis in both tension-stressed and normal tissues in aspen, and that the on/off control of PtCesA expression may be a part of a signaling mechanism triggering a stress-related compensatory deposition of cellulose and lignin that is crucial to growth and development in trees.

Estudio retrospectivo de catéteres endovenosos de larga duración en niños / Retrospective study of prolonged intravenous catheter therapy in children

Los tratamientos endovenosos prolongados, inicialmente, en pacientes oncológicos, requieren de catéteresendovenosos centrales de larga duración. En nuestro hospital, este tipo de tecnología se ha utilizado desde 1989. Presentamos nuestra experiencia con 54 pacientes pediátricos que requirieron catéteres centrales endovenosos, durante los años 1989 y 1997. Se extrajeron datos de las fichas clínicas, concernientes a edad, diagnóstico, tipo de catéteres, ubicación, complicaciones, tiempo de uso del catéter, entre otros

Hidatidosis esplénica: actualización serológica / Splenic hydatidosis: serologic update

Se presenta un caso de hidatidosis esplénica primaria en un menor de 8 años de edad, de procedencia rural, que cursa con síndrome febril y esplenomegalia, cuyo diágnostico presuntivo se estableció mediante imagenología y serología específica. Se realizó tratamiento médico previo a la cirugía para minimizar losriesgos de diseminación.En la terapia quirúrgica, se aspiró el contenido quístico, esterilizando la cabidad con cloruro de sodio hipertónico, dejando un drenaje intraquístico, sin extirpar el bazo. Se comentan los beneficios del tratamiento médico y los avances en el diagnóstico serológico

5-hydroxyconiferyl aldehyde modulates enzymatic methylation for syringyl monolignol formation, a new view of monolignol biosynthesis in angiosperms.

S-Adenosyl-L-methionine-dependent caffeate O-methyltransferase (COMT, EC 2.1.1.6) has traditionally been thought to catalyze the methylation of caffeate and 5- hydroxyferulate for the biosynthesis of syringyl monolignol, a lignin constituent of angiosperm wood that enables efficient lignin degradation for cellulose production. However, recent recognition that coniferyl aldehyde prevents 5-hydroxyferulate biosynthesis in lignifying tissue, and that the hydroxylated form of coniferyl aldehyde, 5-hydroxyconiferyl aldehyde, is an alternative COMT substrate, demands a re-evaluation of the role of COMT during monolignol biosynthesis. Based on recombinant aspen (Populus tremuloides) COMT enzyme kinetics coupled with mass spectrometry analysis, this study establishes for the first time that COMT is in fact a 5-hydroxyconiferyl aldehyde O-methyltransferase (AldOMT), and that 5-hydroxyconiferyl aldehyde is both the preferred AldOMT substrate and an inhibitor of caffeate and 5-hydroxyferulate methylation, as measured by K(m) and K(i) values. 5-Hydroxyconiferyl aldehyde also inhibited the caffeate and 5-hydroxyferulate methylation activities of xylem proteins from various angiosperm tree species. The evidence that syringyl monolignol biosynthesis is independent of caffeate and 5-hydroxyferulate methylation supports our previous discovery that coniferyl aldehyde prevents ferulate 5-hydroxylation and at the same time ensures a coniferyl aldehyde 5-hydroxylase (CAld5H)-mediated biosynthesis of 5-hydroxyconiferyl aldehyde. Together, our results provide conclusive evidence for the presence of a CAld5H/AldOMT-catalyzed coniferyl aldehyde 5-hydroxylation/methylation pathway that directs syringyl monolignol biosynthesis in angiosperms.

Microlaparoscopy with conscious sedation in adolescents with suspected pelvic inflammatory disease.

STUDY OBJECTIVE: To develop a protocol for emergency department microlaparoscopy with conscious sedation in adolescents with clinically suspected pelvic inflammatory disease (PID), and to evaluate the feasibility and tolerability of microlaparoscopy in this population. DESIGN: Prospective study involving adolescents and young adults age 13 to 24 meeting clinical criteria for uncomplicated PID. Laparoscopy subjects underwent microlaparoscopy in the Children's Hospital Emergency Department (ED) and comparison subjects were admitted for treatment of PID. Chi-square, Mann-Whitney U tests, Wilcoxon Rank Sum tests, and repeated measures of analysis of variance (MANOVA) were used for analysis. RESULTS: Twenty-four patients were enrolled: 6 laparoscopy subjects and 18 comparison subjects. Laparoscopy and comparison subjects did not differ with respect to age, mean white blood cell (WBC) count, mean temperature, or mean erythrocyte sedimentation rate. Mean surgical induction time was 13.5 minutes, operative time 19.0 minutes, and total procedure time 32.5 minutes. Mean requirement for midazolam was 2.8 mg and for fentanyl 225 microg. Pain assessment over the first 90 minutes did not differ significantly between laparoscopy and comparison subjects. Four of 6 laparoscopy subjects (67%) and 10 of 18 comparison subjects (56%) were diagnosed with PID (p = NS). CONCLUSIONS: ED microlaparoscopy appears to be feasible, safe, and well tolerated in this small sample of adolescents and young adults with suspected PID.

Secondary xylem-specific expression of caffeoyl-coenzyme A 3-O-methyltransferase plays an important role in the methylation pathway associated with lignin biosynthesis in loblolly pine.

Two types of structurally distinct O-methyltransferases mediate the methylation of hydroxylated monomeric lignin precursors in angiosperms. Caffeate 3-O-methyltransferase (COMT; EC 2.1.1.68) methylates the free acids and caffeoyl CoA 3-O-methyltransferase (CCoAOMT; EC 2.1.1.104) methylates coenzyme A esters. Recently, we reported a novel hydroxycinnamic acid/hydroxycinnamoyl CoA ester O-methyltransferase (AEOMT) from loblolly pine differentiating xylem that was capable of methylating both acid and ester precursors with similar efficiency. In order to determine the possible existence and role of CCoAOMT in lignin biosynthesis in gymnosperms, a 1.3 kb CCoAOMT cDNA was isolated from loblolly pine that showed 79-82% amino acid sequence identity with many angiosperm CCoAOMTs. The recombinant CCoAOMT expressed in Escherichia coli exhibited a significant methylating activity with hydroxycinnamoyl CoA esters whereas activity with hydroxycinnamic acids was insignificant. Moreover, 3.2 times higher catalytic efficiency for methylating caffeoyl CoA over 5-hydroxyferuloyl CoA was observed which could serve as a driving force towards synthesis of guaiacyl lignin. The secondary xylem-specific expression of CCoAOMT was demonstrated using RNA blot analysis, western blot analysis, and O-methyltransferase enzyme assays. In addition, Southern blot analysis indicated that CCoAOMT may exist as a single-copy gene in loblolly pine genome. The transgenic tobacco plants carrying loblolly pine CCoAOMT promoter-GUS fusion localized the site of GUS activity at the secondary xylem tissues. These data suggest that CCoAOMT, in addition to AEOMT, plays an important role in the methylation pathway associated with lignin biosynthesis in loblolly pine.

Ganglioneuroma del torax / Thorax ganglioneuroma

Presentamos el caso clínico de un ganglioneuroma mediastínico en un menor de 12 años de edad, estudiado en cardiología infantil y hematología infantil del Hospital Gustavo Fricke de Viña del Mar. La revisión bibliográfica permite corroborar la rareza de la lesión, la importancia de una buena imagenología para una aproximación diagnóstica y su buen pronóstico al ser extirpados en su totalidad

Conserved sequence motifs in plant S-adenosyl-L-methionine-dependent methyltransferases.

Plant S-adenosyl-L-methionine-dependent methyltransferases (SAM-Mtases) are the key enzymes in phenylpropanoid, flavonoid and many other metabolic pathways of biotechnological importance. Here we compiled the amino acid sequences of 56 SAM-Mtases from different plants and performed a computer analysis for the conserved sequence motifs that could possibly act as SAM-binding domains. To date, genes or cDNAs encoding at least ten distinct groups of SAM-Mtases that utilize SAM and a variety of substrates have been reported from higher plants. Three amino acid sequence motifs are conserved in most of these SAM-Mtases. In addition, many conserved domains have been discovered in each group of O-methyltransferases (OMTs) that methylate specific substrates and may act as sites for substrate specificity in each enzyme. Finally, a diagrammatic representation of the relationship between different OMTs is presented. These SAM-Mtase sequence signatures will be useful in the identification of SAM-Mtase motifs in the hitherto unidentified proteins as well as for designing primers in the isolation of new SAM-Mtases from plants.

A novel multifunctional O-methyltransferase implicated in a dual methylation pathway associated with lignin biosynthesis in loblolly pine.

S-adenosyl-L-methionine (SAM)-dependent O-methyltransferases (OMTs) catalyze the methylation of hydroxycinnamic acid derivatives for the synthesis of methylated plant polyphenolics, including lignin. The distinction in the extent of methylation of lignins in angiosperms and gymnosperms, mediated by substrate-specific OMTs, represents one of the fundamental differences in lignin biosynthesis between these two classes of plants. In angiosperms, two types of structurally and functionally distinct lignin pathway OMTs, caffeic acid 3-O-methyltransferases (CAOMTs) and caffeoyl CoA 3-O-methyltransferases (CCoAOMTs), have been reported and extensively studied. However, little is known about lignin pathway OMTs in gymnosperms. We report here the first cloning of a loblolly pine (Pinus taeda) xylem cDNA encoding a multifunctional enzyme, SAM:hydroxycinnamic Acids/hydroxycinnamoyl CoA Esters OMT (AEOMT). The deduced protein sequence of AEOMT is partially similar to, but clearly distinguishable from, that of CAOMTs and does not exhibit any significant similarity with CCoAOMT protein sequences. However, functionally, yeast-expressed AEOMT enzyme catalyzed the methylation of CAOMT substrates, caffeic and 5-hydroxyferulic acids, as well as CCoAOMT substrates, caffeoyl CoA and 5-hydroxyferuloyl CoA esters, with similar specific activities and was completely inactive with substrates associated with flavonoid synthesis. The lignin-related substrates were also efficiently methylated in crude extracts of loblolly pine secondary xylem. Our results support the notion that, in the context of amino acid sequence and biochemical function, AEOMT represents a novel SAM-dependent OMT, with both CAOMT and CCoAOMT activities and thus the potential to mediate a dual methylation pathway in lignin biosynthesis in loblolly pine xylem.