Complicaciones Asociadas a la Remoción Estética del Cuerpo Adiposo de la Boca (de Bichat) - Revisión Narrativa / Complications Associated with Aesthetic Removal of the Buccal Adipose Body (Bichat's fat-pad) - Narrative Review

El cuerpo adiposo de la boca (CAB) es un componente adiposo multilobulado bien delimitado, localizado de manera bilateral en la región facial íntimamente relacionado a estructuras nerviosas y vasculares. La remoción de CAB es un procedimiento ampliamente estudiado en el campo de la cirugía maxilofacial, utilizado principalmente para cubrir defectos. Su influencia en la estética facial ha iniciado una popularización de la remoción de la extensión bucal de CAB para obtener un rostro más estilizado, intervención difundida como poco invasiva y sin complicaciones. El objetivo de este estudio fue recopilar y evaluar estudios que reporten y evalúen complicaciones asociadas a la remoción por razones estéticas de CAB. Se revisó la evidencia en las bases de datos Medline vía PubMed, Epistemonikos, Scopus y Google Scholar, utilizando términos predefinidos, seleccionando estudios primarios de reportes de casos. Se incluyeron 7 artículos con un total de 10 pacientes; de estos, ocho pacientes se realizaron este procedimiento en Brasil, uno en Estados Unidos y uno en Chile. La distribución de la población fue de 3:7 entre hombres y mujeres con edad promedio de 35 años y un rango entre los 23 a los 49 años. En relación a las complicaciones reportadas, 100 % de los pacientes presentaron asimetría facial, un 80 % presentó edema facial, 30 % manifestaron sialocele, Trismus 20 %, 40 % presentó hematoma, 20 % compromiso del estado general, 20 % presentaron disfagia, en los casos de hipoestesia, parestesia, absceso, seroma, parálisis facial, odinofagia, fiebre se expresaron en 10 % de la población estudiada. En todos los estudios se describió una reintervención quirúrgica posterior a la remoción estética del cuerpo adiposo de bichat. La escasa literatura y la baja calidad de esta, no permite estimar el porcentaje real de posibles complicaciones, tampoco es posible determinar sus resultados a largo plazo ya que no existe en la evidencia un seguimiento apropiado para estos pacientes.

The buccal adipose body (BAB) is a well- defined multilobulated adipose component, located bilaterally in the facial region, closely related to nervous and vascular structures. BAB removal is a widely studied procedure in the field of maxillofacial surgery, used mainly to cover defects. Its influence on facial aesthetics has started to popularize the removal of the BAB buccal extension to obtain a more stylized face, an intervention widely known as minimally invasive and without complications. The objective of this study was to collect and evaluate studies that report and evaluate complications associated with the removal of BAB for cosmetic reasons. The evidence was reviewed in the Medline databases via PubMed, Epistemonikos, Scopus, and Google Scholar, using predefined terms, selecting primary studies from case reports. 7 articles with a total of 10 patients were included; Of these, eight patients underwent this procedure in Brazil, one in the United States, and one in Chile. The distribution of the population was 3:7 between men and women with an average age of 35 years and a range between 23 to 49 years. In relation to the reported complications, 100 % of the patients presented facial asymmetry, 80 % presented facial edema, 30 % manifested sialocele, trismus 20 %, 40 % presented hematoma, 20 % compromised general state, 20 % presented dysphagia, in the cases of hypoesthesia, paresthesia, abscess, seroma, facial paralysis, odynophagia, fever were expressed in 10 % of the studied population. All the studies described a surgical reintervention after cosmetic removal of the bichat adipose body. The scarce literature and its low quality do not allow estimating the real percentage of possible complications, nor is it possible to determine their long-term results since there is no evidence of appropriate follow-up for these patients.

[Quality of spirometry in Primary Care in Cantabria 10 years later. EspiroCan Study]. / Calidad de las espirometrías en Atención Primaria en Cantabria 10 años después. Estudio EspiroCan.

INTRODUCTION: To study the quality of spirometry performed in Primary Care in Cantabria (Spain) and the level of compliance with the regulations of this technique of the Spanish Society of Chest Diseases and Thoracic Surgery (SEPAR). MATERIAL AND METHODS: Cross-sectional descriptive study in the Community of Cantabria using an original questionnaire based on the latest SEPAR regulations. The questionnaire was distributed in 2018 by internal mail to the 42 Primary Care Centres of the Cantabrian Health Service, with the coordinators of the PCC and the nurses responsible having been personally contacted by the researchers or by telephone. This is an original survey, based on the regulations of the SEPAR, which evaluates the quality of the material used (model, years of operation, calibration, cleanliness), as well as the training of personnel who perform spirometry. RESULTS: The health personnel responsible for performing spirometry were surveyed in the 42 Primary Care Centres of the Cantabrian Health Service throughout the Cantabrian area. A mean of 564 spirometries are performed per month. A significant number (13%) of spirometers are never calibrated, and only 10.5% of the spirometers are calibrated by the personnel who perform the test in the centre itself. More than half (54, 53.7%) of these professionals have never received specific training to perform spirometry, and only 3.8% of them have experience in performing the test as recommended by SEPAR. As for the cleaning of the devices, 30% of the technicians do not clean the spirometer or the adapter. CONCLUSIONS: 10 years after our initial study lack of training is still being observed in the professionals, and probably translates into invalid spirometry.

¿Es seguro y efectivo tratar la apendicitis aguda no complicada con antibióticos?- Primera actualización / Are antibiotics a safe and effective treatment for acute uncomplicated appendicitis?- First update

ACTUALIZACIÓN: Este resumen Epistemonikos (Living FRISBEE: Living FRIendly Summary of the Body of Evidence using Epistemonikos) es una actualización del resumen publicado en enero de 2016. INTRODUCCIÓN: La apendicitis es una causa típica de dolor abdominal agudo y la causa más frecuente de cirugía abdominal de urgencia. En las últimas dos décadas se ha publicado creciente evidencia sobre el uso de antibióticos como tratamiento exclusivo de la apendicitis aguda. MÉTODOS: Para responder esta pregunta utilizamos Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante búsquedas en múltiples fuentes de información, incluyendo MEDLINE, EMBASE, Cochrane, entre otras. Extrajimos los datos desde las revisiones identificadas, reanalizamos los datos de los estudios primarios, realizamos un metanálisis y preparamos una tabla de resumen de los resultados utilizando el método GRADE. RESULTADOS Y CONCLUSIONES: Identificamos 23 revisiones sistemáticas que en conjunto incluyeron 28 estudios primarios, de los cuales ocho corresponden a ensayos aleatorizados. Concluimos que el uso exclusivo de antibióticos para el tratamiento de la apendicitis aguda no complicada podría ser menos efectivo que la apendicectomía y asociarse a una mayor estadía hospitalaria, pero por otro lado podría asociarse a una menor tasa de complicaciones.

UPDATE: This Living FRISBEE (Living FRIendly Summary of the Body of Evidence using Epistemonikos) is an update of the summary published in January 2016. INTRODUCTION: Appendicitis is a typical cause of acute abdominal pain and the most frequent cause of emergency abdominal surgery. In the last two decades, increasing evidence has been published about the use of antibiotics as an exclusive treatment for acute appendicitis. METHODS: To answer this question, we used Epistemonikos, the largest database of systematic reviews in health, which is maintained through searches from multiple sources of information, including MEDLINE, EMBASE, Cochrane, among others. We extracted the data from the identified reviews, reanalyzed the data from the primary studies, performed a meta-analysis and prepared a summary of findings table using the GRADE approach. RESULTS AND CONCLUSIONS: We identified 23 systematic reviews including 28 primary studies, of which eight were randomized trials. We concluded the exclusive use of antibiotics for the treatment of uncomplicated acute appendicitis could be less effective than appendectomy, but it might be associated with a lower rate of complications.

A new combined operative technique using crossed inguinal lymphatic rescue for pediatric patients with mixed lymphatic and venous malformations.

Truncular venous malformations and acquired functional or anatomical venous occlusions (or sub-occlusions) can be the cause of secondary lymphedema and even the cause of primary lymphedema when they are associated with lymphatic malformations (lymphangiodysplasia - LAD I, lymphadenodysplasia - LAD II, or a combination of both) in pediatric patients. This understanding recognizes the shared and successive embryogenesis of both systems. These conditions can exhibit hypertension in the venous pedicles intended for lymph-venous anastomosis, and this finding would be a formal contraindication to the procedure. However, this hypertension is a rarely considered condition and is not commonly identified. As a technique to solve this problem, we have combined Nielubowicz, Olszewski, Campisi, and Palma's proposals and created a lymph-venous anastomosis from the side with lymphedema and venous hypertension (lymphatic donor and venous recipient) with an internal suprapubic saphenous venous bridge (from the normal side to the lymphedematous side with venous hypertension) to enable a crossed inguinal lymphatic/venous rescue. We believe this newly synthesized approach will allow better clinical care of pediatric patients with complex and combined lymphatic-venous malformations and is worthy of further investigation.

Physiotherapy in upper limb lymphedema after breast cancer treatment: a randomized study.

Our aim was to compare the responses of physical treatment with or without manual lymphatic drainage (MLD) in lymphedema after breast cancer treatment in a Brazilian population. This was a controlled clinical trial with lymphedema secondary to breast cancer treatment patients that were randomized into either: Group 1 consisting of MLD, skin care, bandaging and remedial exercises; or Group 2 using skin care, bandaging and remedial exercises. Sixty-six patients were randomized and 9 were excluded during the first phase, resulting in a total of 57 patients eligible for analyzes with 28 in Group 1 and 29 in Group 2. The first phase of treatment had an average duration of 24 days (+/- 12.38) and final volume excess average (VE) between limbs was 494.51 ml, corresponding to 29.18% of the initial volume. Volume reduction was highly significant, independent of the intervention (p < 0.001), and both treatments led to an average of percentage volume excess reduction (PVER) of 15.02%. Patients with incomplete range of motion and lymphatic-related fibrotic tissues showed a statistically significant reduction in the percentage of volume excess (p = 0.010; p = 0.009). The presence of arm paresthesia was associated with the lowest therapeutic response (p = 0.024). Both treatment groups demonstrated absolute and relative reductions of excess limb volume, and the addition of MLD did not significantly increase the therapeutic response in women with lymphedema after breast cancer.

Role of balloon postdilation following trancatheter aortic valve implantation.

Paravalvular aortic regurgitation (AR) is a frequent complication following transcatheter aortic valve implantation (TAVI) with an incidence of mild to moderate AR almost systematically higher than 30%. Moreover, several studies have shown that AR has a negative impact on short and mid-term mortality. Balloon postdilation has been proposed as an initial periprocedural option for patients with paravalvular AR to obtain a better expansion of the stent valve frame and potentially reduce the severity of the leak. The aim of this review is to discuss the current available literature on balloon postdilation as a treatment of paravalvular AR after TAVI, its impact on clinical events and future perspectives.

Follicular dynamics, interval to ovulation and fertility after AI in short-term progesterone and PGF2α oestrous synchronization protocol in sheep.

The study was aimed to assess the influence that short-term progesterone treatments have on follicular dynamics, oestrus and ovulation in sheep. The treatment was tested thereafter in a field trial to assess its fertility after AI with fresh semen. In a first experiment, 12 ewes without CL were grouped to receive a new (n = 6) or used CIDR (n = 6) for 7 days and blood samples were obtained to follow plasma progesterone profiles. In a second experiment, 39 cycling ewes were synchronized by a 7-day P4+PGF2α protocol using a new (n = 20) or a 7-day used CIDR (n = 19). Half of both groups received 400 IU eCG and half remained untreated as controls. Ultrasound ovarian examination and oestrous detection were used to compare follicular dynamics, oestrus and ovulation in both groups. In a third experiment, 288 ewes in 3 farms were synchronized by the short-term P4+PGF2α+eCG protocol and ewes were AI with fresh semen 24 h after oestrous detection. Lambing performance was used to test the fertility of the treatment. In Experiment 1, ewes with new inserts presented higher P4 concentration than ewes with used inserts throughout the sampling period (p < 0.05) and exhibited a P4 peak at days 1-2 of the treatment that was not observed in ewes with used inserts. In Experiment 2, ewes treated with new and used inserts show similar ovarian and behavioral traits (p > 0.10). However, ewes treated with eCG show shorter interval to oestrus (p = 0.004) and tend to have larger mature CL (p = 0.06). In Experiment 3, oestrous presentation and lambing performance after AI with fresh semen was considered normal compared to published results. Results suggest that the oestrous synchronization protocol based on P4+PGF2α allows little control of follicular dynamics without compromising fertility after AI with fresh semen provided that eCG is added at the end of the treatment.

Pilot-scale production and liquid formulation of Rhodotorula minuta, a potential biocontrol agent of mango anthracnose.

AIMS: To develop a pilot-plant fermentation process for the production of the yeast Rhodotorula minuta, to be used as a biocontrol agent of mango anthracnose, using a low-cost culture medium. To develop a stable liquid formulation that preserve high viability of the yeast stored at 4 degrees C. METHODS AND RESULTS: Keeping constant the volumetric power input, a fermentation process was scaled-up from shake flasks to a 100 l bioreactor. Preharvest applications of the yeast resulted in postharvest anthracnose severity equal or lower than that observed with a chemical fungicide. Glycerol was added to the formulation as water activity reducer and xanthan gum as a viscosity-enhancing agent. Yeast initial concentration of 10(10) CFU ml(-1) resulted in 4-5 orders of magnitude decrease after 1 month of storage at 4 degrees C, whereas when it was formulated at 10(9) CFU ml(-1), the decrease was of two orders of magnitude in 6 months. CONCLUSIONS: The fermentation process was successfully scaled-up using a low-cost culture medium. Postharvest anthracnose severity could be considerably reduced using this yeast. Formulating the yeast at 10(9) CFU ml(-1) and adding glycerol (20%) and xanthan (5 g l(-1)) avoided both contamination and yeast sedimentation and it was able to preserve up to 10(7) CFU ml(-1) after 6 months at 4 degrees C. SIGNIFICANCE AND IMPACT OF THE STUDY: The yeast R. minuta is reported as a novel antagonistic micro-organism against the pathogen Colletotrichum gloeosporioides. Pilot plant production of this yeast allowed us to conduct field tests in commercial orchards during three harvest seasons. Yeast suspensions applied to mango trees reduced the fruit anthracnose severity in levels similar or better than chemical fungicides.

[Diagnostic accuracy of the SPECT of post-stress myocardial perfusion with attenuation and scatter correction]. / Exactitud diagnóstica de la SPET de perfusión miocárdica postesfuerzo con corrección de atenuación y de dispersión.

OBJECTIVE: To evaluate the effect of attenuation and scatter correction (AC-SC) on the diagnostic accuracy of post-stress myocardial perfusion (MP) SPECT. MATERIAL AND METHODS: The retrospective analysis included 121 patients who had a non-corrected (NC) and AC-SC 99mTc-Tetrofosmin MP SPECT after stress. The left ventricle was divided into 13 segments. Two observers performed a visual assessment of the MP on a scale from 0 (perfusion defect) to 3 (normal uptake). A consensus on concordances and discordances between the NC and AC-SC images was established. Final diagnosis of coronary artery disease (CAD) was established by coronary angiography (CANG) (stenosis > or = 70 %). RESULTS: The combined analysis of NC and AC-SC images produced 93 concordances and 28 discordances. Of the 93 concordances, both studies were abnormal in 67 patients (abnormal CANG in 57) and normal in 26 patients (normal CANG in 20). Among the 28 discordances, 23 were abnormal NC/normal AC-SC (normal CANG in 18) and 5 normal NC/abnormal AC-SC. In these 5 patients AC-SC generated anterior perfusion defects but the CANG was normal. Overall, the appearance of NC and AC-SC images were in agreement with the CANG findings in the 72 % (87/121) and 78 % (95/121) of the patients, respectively. Sixty-seven of the 90 patients with abnormal NC had also abnormal AC-SC (abnormal CANG in 57) and the other 23 had normal AC-SC (normal CANG in 18). The appearance of AC-SC was in agreement with CANG finding in the 83 % (75/90) of patients with abnormal NC. MP abnormalities in NC normalized by AC-SC were more frequently located in inferior wall CONCLUSION: AC-SC improves the diagnostic accuracy of post stress NC MP SPECT for the diagnosis of CAD. From these results we consider that AC-SC is of clinical value for the correction of attenuation artifacts, more frequently observed in the inferior wall. The presence of antero-apical perfusion defects in AC-SC with normal NC does not mean CAD. So it is necessary to adjust the normalcy pattern of MP SPECT when AC-SC is performed.

[Scintigraphic image in a case of atypical presentation of Burkitt lymphoma. The role of the scintigraphy with 67Ga SPECT in the diagnosis and post-treatment control]. / Imagen gammagráfica en un caso de presentación atípica de linfoma de Burkitt. El papel de la gammagrafía con Ga67 SPECT en el diagnóstico y control postratamiento.

We present a case of Burkitt's disease with bone (thoracic wall, femur) and lymph node involvement. The patient had symptoms of fever with thoracic wall and femur pain. Lymph node involvement was detected by clinical exploration. A chest X-ray showed rib abnormalities. 99mTc-DPD scan showed thoracic wall (one rib) and femur involvement. 67Gallium SPECT and CT were performed at diagnosis. 67Gallium SPECT showed thoracic wall (one rib more) and abdominal lymph node involvement that was not detected by planar images. A CT scan did not show metastatic disease in mediastinal and abdominal lymph node chains but did show it in one rib and femur. After 6 chemotherapy sessions a new 67gallium scan and CT scan were performed. 67Gallium SPECT showed involvement in the thoracic wall (one rib) that was not detected in planar images. The CT scan was considered normal.

Vesicular stomatitis virus infection and neuropathogenesis in the murine model are associated with apoptosis.

This study examines apoptosis and viral neuropathogenesis in a murine model infected with vesicular stomatitis virus (VSV). VSV induces apoptotic cell death in cultured cell lines, raising the possibility that apoptosis of infected neurons and other target cells may contribute to disease and mortality. To determine whether or not VSV induces apoptosis in neural tissues, mice were inoculated intranasally with VSV. At 24, 48, 72, 96, and 120 hours postinfection, brain tissues were assayed for the presence of viral RNA by in situ hybridization and viral antigen by immunohistochemistry. Apoptosis was identified by in situ terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling and electron microscopy. Viral replication and lesions were observed predominantly in central nervous system neurons. Apoptotic cell death was restricted to the same regions of the brain in which infected cells and tissue injury were identified. Results suggest that VSV-induced apoptosis is a mechanism causing cell death, tissue injury, and mortality in VSV-infected mice.

Prospective clinical comparison of non-corrected and attenuation- and scatter-corrected myocardial perfusion SPECT in patients with suspicion of coronary artery disease.

Attenuation artefacts decrease the specificity of myocardial perfusion single-photon emission computed tomography (SPECT). In this paper, the results of a prospective study evaluating the clinical applicability of attenuation and scatter correction in myocardial perfusion SPECT are presented. Of 607 patients in whom post-stress 99mTc-tetrofosmin myocardial perfusion SPECT was performed due to suspicion of coronary artery disease, 99 also underwent coronary angiography (CAG). A simultaneous emission/transmission acquisition was performed. A multiple linear array of 153Gd sources and four independent energy windows were used for attenuation and scatter correction. A blind separate analysis of non-corrected (NC) and attenuation- and scatter-corrected (AC-SC) images was performed with scores of zero (no uptake) to three (normal uptake). The final diagnosis was based on CAG findings, and stenoses of > or =70% were considered to be significant. NC images had a sensitivity of 92% and a specificity of 46%. In AC-SC images, the sensitivity decreased to 76%, but the specificity increased to 71%. The decrease in the sensitivity of AC-SC images was observed in all three coronary regions. Attenuation and scatter correction increased the specificity in the right coronary region, but decreased the specificity in the left anterior descending coronary region. In 13 of the 99 patients, AC-SC images showed false positive findings due to count deficiency in the anterior wall with normal CAG. The size of perfusion defects was decreased in AC-SC images (from 5.01 +/- 2.74 to 3.15 +/- 2.50 segments). The severity of perfusion defects was higher in NC (1.10 +/- 0.60) than in AC-SC (1.28 +/- 0.56) images. The combined evaluation of NC and AC-SC images was in agreement with the CAG findings in 79% of patients. It can be concluded that, when compared with NC images, AC-SC images improved the specificity in the right coronary region and decreased the sensitivity in all three coronary regions. Attenuation and scatter correction may generate anterior wall defects with normal CAG. The analysis of AC-SC images cannot be used alone for the diagnosis of coronary artery disease. In the clinical setting, combined NC and AC-SC images are recommended for the evaluation of post-stress myocardial perfusion SPECT.

[Bone scintigraphy in Erdheim-Chester disease]. / Gammagrafía ósea en la enfermedad de Erdheim-Chester.

Erdheim-Chester disease (ECD) is a rare disorder with fewer than 80 cases reported in the world. It consists of a non-Langerhans' cell histiocytosis that usually presents as pain due to bone involvement; however, the prognosis is marked by extraskeletal involvement. Although the final diagnosis needs an anatomophatologic study (normally through a bone biopsy), radiologic and scintigraphic findings are quasi pathognomonic. In this work, we report 2 ECD cases and their respective bone scans showing typical findings described in the literature. We found bilateral and symmetrical increased uptake of diaphyses and metaphyses of long bones, mainly in lower limbs. The mid-diaphyses and the epiphyses (partially in the first case) as well as the axial skeleton are spared.

[Effect of attenuation correction and scatter compensation on the 99mTc-MIBI myocardial perfusion spect in patients without coronary artery disease]. / Efecto de la corrección de la atenuación y de la radiación dispersa en la SPET de perfusión miocárdica con 99mTc-MIBI de pacientes sin cardiopatía isquémica.

OBJECTIVE: Attenuation correction (AC) and scatter compensation (SC) techniques are recent developments of myocardial perfusion SPECT. Our aim was to evaluate the effect of AC + SC on the myocardial distribution of 99mTc-MIBI in a population without coronary artery disease. MATERIAL AND METHODS: A multiarray of Gd-153 linear sources was used for simultaneous transmission/emission 99mTc-MIBI myocardial perfusion SPECT in 27 patients without coronary artery disease. A visual analysis and polar map quantification was performed. Changes between non-corrected (NC) and corrected (AC + SC) studies were compared. RESULTS: AC + SC produced an increase in liver activity and better visualization of the right ventricle. Intestinal activity increased in six patients. Myocardial homogeneity was increased by AC + SC. No differences by gender were observed after AC + SC. In females AC + SC led to a decrease of uptake in the anterior wall, apex and apical segments of the lateral wall and septum, and an increase in the inferior wall. In males AC + SC caused an increase of uptake in the inferior wall and in the basal segments of septum and a decrease of uptake in apex and apical segments of anterior and lateral walls. AC + SC generated false defects in the anterior wall of five patients. CONCLUSIONS: Our results show the usefulness of AC + SC for compensating the interferences produced by attenuation on the myocardial distribution of 99mTc-MIBI. Because AC + SC may introduce false defects, it must not be applied to normal perfused myocardium.

[Clinical significance of the increased uptake of a solitary rib lesion in the bone scintigraphy. Based on an osteoblastoma]. / Significado clínico de la hipercaptación costal única en la gammagrafía ósea. A propósito de un osteoblastoma.

A case of a bone tumor located in the right sixth rib detected by means of the bone scan as a solitary lesion is presented. Although the chest X-ray and CT were normal, a low signal intensity on T1 images and high-intensity on T2 images were seen in the MRI. The post-surgical histological diagnosis was osteoblastoma. A review of the clinical significance of solitary rib lesions which appear with increased uptake on bone scan was performed. When a differential diagnosis is made of a solitary rib lesion that appears on a bone scan, osteoblastoma should be considered.

Porcine reproductive and respiratory syndrome virus: description of persistence in individual pigs upon experimental infection.

We studied the persistence of porcine reproductive and respiratory syndrome virus (PRRSV) in individual experimentally infected pigs, during a period of up to 150 days postinfection (dpi). The results of this study suggest that the persistence of PRRSV involves continuous viral replication but that it is not a true steady-state persistent infection. The virus eventually clears the body and seems to do it in most of the animals by 150 dpi or shortly thereafter. High genetic stability was seen for several regions of the persistent PRRSV's genome, although some consistent mutations in the genes of envelope glycoproteins and M protein were also observed.

North American and European porcine reproductive and respiratory syndrome viruses differ in non-structural protein coding regions.

Although North American and European serotypes of porcine reproductive and respiratory syndrome virus (PRRSV) are recognized, only the genome of the European Lelystad strain (LV) has been sequenced completely. Here, the genome of the pathogenic North American PRRSV isolate 16244B has been sequenced and compared with LV. The genomic organization of 16244B was the same as LV but with only 63.4% nucleotide identity. The 189 nucleotide 5' non-coding region (NCR) of 16244B was distinct from the LV NCR, with good conservation (83%) only over a 43 base region immediately upstream of open reading frame (ORF) 1a. Major differences were found in the region encoding the non-structural part of the ORF1a polyprotein, which shared only 47% amino acid identity over 2503 residues of the six non-structural proteins (Nsps) encoded. Nsp2, thought to have a species-specific function, showed the greatest divergence, sharing only 32% amino acid identity with LV and containing 120 additional amino acids in the central region. Nsps encoded by the 5'-proximal and central regions of ORF1b had from 66 to 75% amino acid identity; however, the carboxy-terminal protein CP4 was distinct (42% identity). The ORF 1a-1b frameshift region of 16244B had 98% nucleotide identity with LV. Consistent with previous reports for North American isolates, the six structural proteins encoded were 58 to 79% identical to LV proteins. The 3' NCR (150 nucleotides) was 76% identical between isolates. These genomic differences confirm the presence of distinct North American and European PRRSV genotypes.

Angiostatin suppresses malignant glioma growth in vivo.

Human malignant gliomas are among the most malignant and most intensely vascularized solid tumors. Angiostatin, an internal fragment of plasminogen, was recently discovered as an endogenous inhibitor of tumor-related angiogenesis by selective inhibition of endothelial cell growth. Using xenograft transplants of rat and primary human glioma cells in immunodeficient mice we investigated the effects of systemic administration of angiostatin purified from human plasma on tumor growth. The rat C6 and 9L glioma and the human U87 glioma cell lines implanted either s.c. or intracranially in Swiss nude mice responded to angiostatin in a dose-dependent fashion with growth inhibition to 11% of controls (P < 0.01), without detectable signs of toxicity. The inhibition of treated tumors was accompanied by a marked reduction of vascularity to 38% of controls (P < 0.01) in the presence of an up to 6-fold increased apoptotic index (P < 0.01), consistent with the hypothesis that angiostatin acts tumoristatic by inhibiting tumor-induced endothelial cell proliferation. Expression analysis of growth factors in angiostatin-treated tumors revealed an up to 3-fold decrease in vascular endothelial growth factor-mRNA and an up to 4-fold increase in basic fibroblast growth factor-mRNA, as compared with untreated controls in rat gliomas (P < 0.01). This suggests that inhibition of the tumorigenic phenotype may be mediated in part by a downregulation of vascular endothelial growth factor expression within the tumor. Our data demonstrate that systemic administration of angiostatin efficiently suppresses malignant glioma growth in vivo. The tumoristatic activity against intracranial tumors independent of the blood brain barrier suggests that targeting the vascular compartment may offer novel therapeutic strategies against malignant gliomas.