Identification of a new small bioactive peptide from Lactobacillus gasseri supernatant.

Ten lactic acid bacteria (LAB) strains, previously isolated from human ileal biopsy of healthy volunteers, were screened for production and secretion of molecules having anti-bacterial and anti-biofilm activities. Because many recent reports indicate that LAB secreted molecules may exert immune-modulatory action, we also tested the effect on human intestinal HCT116 cells challenged with bacterial lipopolysaccharides. One of the Lactobacillus gasseri strains, SF1109, strongly inhibited: (1) Pseudomonas aeruginosa growth; (2) Escherichia coli biofilm production; (3) LPS induction of P-ERK1/2 in HCT116 cells, and was selected for further characterisation of the secreted active molecule. Cell-free supernatant of the L. gasseri SF1109 was analysed and one 1.3 kDa peptide has been characterised. Eight out twelve amino acids of this peptide were identified allowing the synthesis of an octa-peptide which still presented the mentioned activities.

Bloqueo nervioso lumbar selectivo guiado por tomografía computada. Nuestra experiencia en un hospital universitario / Computed tomography guided selective lumbar nerve block. Our experience in a university hospital

Objetivos: Presentar nuestra experiencia en el tratamiento mínimamente invasivo de la lumbociatalgia con la inyección de corticoides y anestésicos locales bajo control tomográfico. Materiales y métodos: Se realizaron bloqueos selectivos lumbares bajo control tomográfico a 102 pacientes con lumbociatalgia crónica, en un período comprendido entre agosto del 2011 y junio del 2012. Del total de pacientes, se infiltraron 65 a nivel foraminal (64%), 29 a nivel epidural (28%) y 8 a ambos niveles (8%). Los procedimientos se realizaron en forma ambulatoria con anestesia local. Todos los pacientes recibieron tratamiento con antiinflamatorios no esteroides (AINES) vía oral y se utilizó la escala numérica del dolor y el índice de Oswestry (IDO) para medir la discapacidad funcional en cada caso. Resultados: El 100% de los pacientes mostró disminución significativa de la sintomatología apenas finalizó el procedimiento, sin observarse complicaciones inmediatas durante el mismo. Se hizo un seguimiento clínico posterior con las escalas anteriormente mencionadas a los 7 días, 1, 3 y 6 meses. En 95 pacientes (93%) se observó una mejora significativa de los síntomas y se suspendió o se redujo la medicación oral, mientras que en 6 pacientes existió una mejoría parcial de los síntomas al mes, pero hubo una recaída a los 3 meses. En estos casos se debió reiniciar el tratamiento con AINES, manteniéndose a 4 pacientes dentro de la categoría del IDO anterior (aunque con una disminución de al menos 2 puntos en el score numérico del dolor). Sólo un paciente no presentó mejoría de la sintomatología durante el seguimiento y tuvo reaparición de los síntomas habituales a los 7 días, por lo que se debió reprogramar una segunda infiltración. Conclusión: En nuestra experiencia el bloqueo nervioso lumbar selectivo bajo control tomográfico, utilizando esteroides y anestésicos locales, resultó un procedimiento efectivo en el control del dolor con un bajo índice de complicaciones.

Objectives: To present our experience with minimally invasive treatment of low back pain and sciatica with the computed tomography-guided percutaneous injection of steroids and local anaesthetics.Materials and methods: From August 2011 to June 2012, 102 patients underwent selective computed tomography-guided foraminal block for low back pain and sciatica treatment.Sixtyfi ve patients received foraminal infi ltration (64%), 29 epidural infi ltration (28%), and 8 (8%) were subject to combined procedures. All procedures were performed on an outpatient basis with local anaesthetic, with no immediate complications. All patients received oral NSAIDs (non-steroidal anti-infl ammatory drugs) prior to the procedure. A numeric scale of pain and the Oswestry index (IDO) was employed to measure local pain and limb disability. All patients showed at least 7 points in the initial evaluation. Results: All the patients showed a significant reduction in pain by the end of procedure.A clinical follow-up was made after 7 days, 1, 3, and 6 months after the treatment using the previously mentioned scales. Ninety-fi ve patients (93%) showed a signifi cant improvement in their symptoms, with suspension or decrease in oral medication. Six patients showed only a partial reduction of symptoms during the follow-up after one month, with a recurrence of symptoms after 3 months and restarted oral treatment. Four of these patients remained in the same IDO category with at least a 2 point decrease in the pain scale. Only one patient showed no improvement in symptoms during follow-up with a recurrence of symptoms 7 days after procedure, and for whom a second procedure was reprogrammed. Conclusion: In our experience CT-guided percutaneous lumbar selective nerve block using steroids and local anaesthetics, is an effective method of pain control with a very low incidence of complications...

Ecografía y biopsia prostéticas en la detección del carcinoma prostético / Prostate ultrasound and biopsy in the detection of prostate carcinoma

Objetivo: Mostrar nuestra experiencia en ecografía prostática transrectal y biopsia prostática bajo guía ecográfica a lo largo de 10 años, a través de la realización de un análisis retrospectivo, con el fin de evaluar sus beneficios en la detección del adenocarcinoma, identificar la distribución de muestras positivas en la glándula y exponer la utilidad de la punción de imágenes nodulares. prostáticas transrectales seguidas de biopsias prostáticas bajo control ecográfico. En la muestra se incluyó a pacientes que se realizaron más de una biopsia. Los datos obtenidos de estos procedimientos permitieron identificar la presencia de tres grupos etarios de acuerdo a la incidencia de la patología, conocer la localización más frecuente del adenocarcinoma dentro de la próstata y evaluar la utilidad de la biopsia de los nódulos prostáticos en la detección del adenocarcinoma. Resultados: El análisis de la muestra arrojó un porcentaje de detección del adenocarcinoma del 16% en los menores de 50 años, del 36% en aquellos entre los 50 y 60 años, y del 48% en los mayores de 65 años. La base izquierda de la próstata fue la localización con el índice más alto de positividad (15%), seguido por la media izquierda (14%), la base derecha (14%), la media derecha (13%), el ápex izquierdo (12%), el medio lateral izquierdo (12%), el ápex derecho (11%) y el medio lateral derecho (10%). Doscientos noventa y nueve pacientes presentaron imágenes nodulares: 118 (Grupo A) tuvieron alguna muestra positiva y 181 presentaron resultados negativos (Grupo B). A su vez, el Grupo A se dividió en 3 subgrupos: el Subgrupo A, cuyo resultado positivo se registró en la muestra del nódulo, pero fue negativo en el resto de la glándula; Subgrupo B, cuyos resultados fueron positivos en el resto de la glándula y negativos en la muestra del nódulo; y Subgrupo C, cuyo resultado fue positivo tanto en las muestras de la glándula como en las del nódulo (combinación más frecuente de los tres subgrupos). Conclusión: La ecografía y la biopsia prostáticas bajo guía ecográfi ca juegan un rol importante en la evaluación de la próstata ante la sospecha de un adenocarcinoma. Según nuestra experiencia, la biopsia prostática bajo guía ecográfi ca es el método de mayor utilidad para la detección, especialmente en pacientes mayores de 65 años, y debería incluirse la muestra del nódulo (si la hubiese) en el esquema por octantes.

Purpose: To present our experience in prostatic transrectal ultrasound and transrectal ultrasound-guided biopsy over a ten-year period by a retrospective analysis in order to determine the detection rate of adenocarcinoma, identify the distribution of positive samples in the gland, and evaluate the usefulness of biopsy of nodules seen on imaging studies. Materials and methods: A total of 1163 ultrasound and ultrasound-guided transrectal prostate biopsies were performed between March 2001 and November 2011. The population sample included patients who had more than one biopsy performed. Data obtained from these procedures enables us to identify three age groups according to the incidence of pathology, to determine the most frequent location of adenocarcinoma within the prostate, and to evaluate the usefulness of prostate nodules biopsy in the detection of adenocarcinoma. Results: The data analysis showed a 16% detection rate of adenocarcinoma in men under 50 years of age, 36% in patients between 50 and 65 years, and 48% in patients older than 65 years. The left base of the prostate had the highest detection rate (15%), followed by left medium (14%), right base (14%), right medium (13%), left apex (12%), left lateral medium (12%), right apex (11%) and right lateral medium (10%). Nodular images were found in 299 patients: 118 were positive for adenocarcinoma (Group A) and 181 were negative (Group B). Group A was divided into 3 subgroups: Subgroup A, with a positive result only in the nodule sample, and a negative result in the rest of the gland sample; Subgroup B, with a positive result in the gland samples but negative in the nodule sample; and Subgroup C, with results that were positive both in the gland and nodule samples. Conclusion: Ultrasound and ultrasound-guided transrectal prostate biopsy play an important role in the evaluation of the prostate when adenocarcinoma is suspected. Based on our experience, ultrasound-guided prostate biopsy is the most useful method for the detection of adenocarcinoma, especially in patients older than 65 years of age, and the nodule sample (if any) should be included in the eight-biopsy scheme.

Bloqueo nervioso lumbar selectivo guiado por tomografía computada. Nuestra experiencia en un hospital universitario / Computed tomography guided selective lumbar nerve block: Our experience in a university hospital

Objetivos: Presentar nuestra experiencia en el tratamiento mínimamente invasivo de la lumbociatalgia con la inyección de corticoides y anestésicos locales bajo control tomográfico. Materiales y métodos: Se realizaron bloqueos selectivos lumbares bajo control tomográfico a 102 pacientes con lumbociatalgia crónica, en un período comprendido entre agosto del 2011 y junio del 2012. Del total de pacientes, se infiltraron 65 a nivel foraminal (64%), 29 a nivel epidural (28%) y 8 a ambos niveles (8%). Los procedimientos se realizaron en forma ambulatoria con anestesia local. Todos los pacientes recibieron tratamiento con antiinflamatorios no esteroides (AINES) vía oral y se utilizó la escala numérica del dolor y el índice de Oswestry (IDO) para medir la discapacidad funcional en cada caso. Resultados: El 100% de los pacientes mostró disminución significativa de la sintomatología apenas finalizó el procedimiento, sin observarse complicaciones inmediatas durante el mismo. Se hizo un seguimiento clínico posterior con las escalas anteriormente mencionadas a los 7 días, 1, 3 y 6 meses. En 95 pacientes (93%) se observó una mejora significativa de los síntomas y se suspendió o se redujo la medicación oral, mientras que en 6 pacientes existió una mejoría parcial de los síntomas al mes, pero hubo una recaída a los 3 meses. En estos casos se debió reiniciar el tratamiento con AINES, manteniéndose a 4 pacientes dentro de la categoría del IDO anterior (aunque con una disminución de al menos 2 puntos en el score numérico del dolor). Sólo un paciente no presentó mejoría de la sintomatología durante el seguimiento y tuvo reaparición de los síntomas habituales a los 7 días, por lo que se debió reprogramar una segunda infiltración. Conclusión: En nuestra experiencia el bloqueo nervioso lumbar selectivo bajo control tomográfico, utilizando esteroides y anestésicos locales, resultó un procedimiento efectivo en el control del dolor con un bajo índice de complicaciones.(AU)

Objectives: To present our experience with minimally invasive treatment of low back pain and sciatica with the computed tomography-guided percutaneous injection of steroids and local anaesthetics. Materials and methods: From August 2011 to June 2012, 102 patients underwent selective computed tomography-guided foraminal block for low back pain and sciatica treatment. Sixtyfi ve patients received foraminal infi ltration (64%), 29 epidural infi ltration (28%), and 8 (8%) were subject to combined procedures. All procedures were performed on an outpatient basis with local anaesthetic, with no immediate complications. All patients received oral NSAIDs (non-steroidal anti-infl ammatory drugs) prior to the procedure. A numeric scale of pain and the Oswestry index (IDO) was employed to measure local pain and limb disability. All patients showed at least 7 points in the initial evaluation. Results: All the patients showed a significant reduction in pain by the end of procedure. A clinical follow-up was made after 7 days, 1, 3, and 6 months after the treatment using the previously mentioned scales. Ninety-fi ve patients (93%) showed a signifi cant improvement in their symptoms, with suspension or decrease in oral medication. Six patients showed only a partial reduction of symptoms during the follow-up after one month, with a recurrence of symptoms after 3 months and restarted oral treatment. Four of these patients remained in the same IDO category with at least a 2 point decrease in the pain scale. Only one patient showed no improvement in symptoms during follow-up with a recurrence of symptoms 7 days after procedure, and for whom a second procedure was reprogrammed. Conclusion: In our experience CT-guided percutaneous lumbar selective nerve block using steroids and local anaesthetics, is an effective method of pain control with a very low incidence of complications.(AU)

Ecografía y biopsia prostéticas en la detección del carcinoma prostético / Prostate ultrasound and biopsy in the detection of prostate carcinoma

Objetivo: Mostrar nuestra experiencia en ecografía prostática transrectal y biopsia prostática bajo guía ecográfica a lo largo de 10 años, a través de la realización de un análisis retrospectivo, con el fin de evaluar sus beneficios en la detección del adenocarcinoma, identificar la distribución de muestras positivas en la glándula y exponer la utilidad de la punción de imágenes nodulares. prostáticas transrectales seguidas de biopsias prostáticas bajo control ecográfico. En la muestra se incluyó a pacientes que se realizaron más de una biopsia. Los datos obtenidos de estos procedimientos permitieron identificar la presencia de tres grupos etarios de acuerdo a la incidencia de la patología, conocer la localización más frecuente del adenocarcinoma dentro de la próstata y evaluar la utilidad de la biopsia de los nódulos prostáticos en la detección del adenocarcinoma. Resultados: El análisis de la muestra arrojó un porcentaje de detección del adenocarcinoma del 16% en los menores de 50 años, del 36% en aquellos entre los 50 y 60 años, y del 48% en los mayores de 65 años. La base izquierda de la próstata fue la localización con el índice más alto de positividad (15%), seguido por la media izquierda (14%), la base derecha (14%), la media derecha (13%), el ápex izquierdo (12%), el medio lateral izquierdo (12%), el ápex derecho (11%) y el medio lateral derecho (10%). Doscientos noventa y nueve pacientes presentaron imágenes nodulares: 118 (Grupo A) tuvieron alguna muestra positiva y 181 presentaron resultados negativos (Grupo B). A su vez, el Grupo A se dividió en 3 subgrupos: el Subgrupo A, cuyo resultado positivo se registró en la muestra del nódulo, pero fue negativo en el resto de la glándula; Subgrupo B, cuyos resultados fueron positivos en el resto de la glándula y negativos en la muestra del nódulo; y Subgrupo C, cuyo resultado fue positivo tanto en las muestras de la glándula como en las del nódulo (combinación más frecuente de los tres subgrupos). Conclusión: La ecografía y la biopsia prostáticas bajo guía ecográfi ca juegan un rol importante en la evaluación de la próstata ante la sospecha de un adenocarcinoma. Según nuestra experiencia, la biopsia prostática bajo guía ecográfi ca es el método de mayor utilidad para la detección, especialmente en pacientes mayores de 65 años, y debería incluirse la muestra del nódulo (si la hubiese) en el esquema por octantes.(AU)

Purpose: To present our experience in prostatic transrectal ultrasound and transrectal ultrasound-guided biopsy over a ten-year period by a retrospective analysis in order to determine the detection rate of adenocarcinoma, identify the distribution of positive samples in the gland, and evaluate the usefulness of biopsy of nodules seen on imaging studies. Materials and methods: A total of 1163 ultrasound and ultrasound-guided transrectal prostate biopsies were performed between March 2001 and November 2011. The population sample included patients who had more than one biopsy performed. Data obtained from these procedures enables us to identify three age groups according to the incidence of pathology, to determine the most frequent location of adenocarcinoma within the prostate, and to evaluate the usefulness of prostate nodules biopsy in the detection of adenocarcinoma. Results: The data analysis showed a 16% detection rate of adenocarcinoma in men under 50 years of age, 36% in patients between 50 and 65 years, and 48% in patients older than 65 years. The left base of the prostate had the highest detection rate (15%), followed by left medium (14%), right base (14%), right medium (13%), left apex (12%), left lateral medium (12%), right apex (11%) and right lateral medium (10%). Nodular images were found in 299 patients: 118 were positive for adenocarcinoma (Group A) and 181 were negative (Group B). Group A was divided into 3 subgroups: Subgroup A, with a positive result only in the nodule sample, and a negative result in the rest of the gland sample; Subgroup B, with a positive result in the gland samples but negative in the nodule sample; and Subgroup C, with results that were positive both in the gland and nodule samples. Conclusion: Ultrasound and ultrasound-guided transrectal prostate biopsy play an important role in the evaluation of the prostate when adenocarcinoma is suspected. Based on our experience, ultrasound-guided prostate biopsy is the most useful method for the detection of adenocarcinoma, especially in patients older than 65 years of age, and the nodule sample (if any) should be included in the eight-biopsy scheme.(AU)

Expression of angiogenesis factors and selected vascular wall matrix proteins in intracranial saccular aneurysms.

OBJECTIVE: Little is known about the biological mechanisms associated with the genesis, growth, and rupture of intracranial saccular aneurysms. It is postulated that the vascular wall pathological response of aneurysmal disease is associated with abnormal angiogenesis factor expression. METHODS: We have examined the expression and distribution of immunoreactivity to angiogenesis growth factors (vascular endothelial growth factor and basic fibroblast growth factor) and selected vascular wall matrix proteins (fibronectin, Type IV collagen, and alpha smooth muscle actin) in the walls of human intracranial aneurysms from surgical biopsy or autopsy specimens. Double antibody immunohistochemical stains were performed in contiguous fixed sections from three control circle of Willis arteries, five berry aneurysms, four giant aneurysms, and one mycotic aneurysm (three unruptured and seven ruptured lesions). RESULTS: The aneurysmal wall exhibited diffuse disorganized expression of matrix proteins as compared to their organization in control vessels. There was strong patchy expression of vascular endothelial growth factor within the walls of all aneurysms, including marked staining of capillaries and small vessels within the thickened walls of giant lesions. The expression of basic fibroblast growth factor was more diffuse and occurred around the fibrocytes and myocytes within the disrupted media of 9 of 10 aneurysms. CONCLUSIONS: These results confirm the gross architectural molecular disruption in the walls of intracranial aneurysms and illustrate an apparent biological response involving angiogenesis factors. Further research should elucidate the time course and possible causal relationships of these changes to aneurysm growth and rupture with the aim of possible therapeutic manipulation.

Clinical neurosciences in the decade of the brain: hypotheses in neuro-oncology. VEG/PF acts upon the actin cytoskeleton and is inhibited by dexamethasone: relevance to tumor angiogenesis and vasogenic edema.

HYPOTHESIS: We have proposed that VEG/PF acts by transforming the cytoskeletal architecture of microvascular endothelial cells. BACKGROUND: Evidence supporting a pivotal role for vascular endothelial growth/permeability factor (VEG/PF) in tumor angiogenesis and edemagenesis is compelling. VEG/PF exhibits specific endothelial cell mitogenicity and is expressed by brain tumors exhibiting increased vascularity and microvascular extravasation. The mechanistic cascade that follows VEG/PF-tyrosine kinase receptor binding remains uncertain, however. Actin is a cytoskeletal protein that regulates cellular motility, shape and vesicular transport. Regulation of actin stress fibers, cell-surface focal adhesions and plasmalemmal "ruffles" is mediated by tyrosine kinase activation of GTP-binding proteins that are in turn linked to intracellular calcium flux. As VEG/PF is known to induce cytosolic calcium ion transients in endothelial cells, actin microfilaments would appear to be logical candidates for study of a cytocontractile response mediated by calcium signal transduction. METHODS: VEG/PF-induced endothelial actin cytoskeletal changes were studied using rhodamine phalloidin staining and fluorescence photomicrography. RESULTS: When exposed to VEG/PF, cultured endothelial cells from human umbilical veins and rat brain microvessels exhibited a reversible, dose-related reorganization of actin stress fibers, cell contraction and rounding, and widening of the intercellular spaces. VEG/PF perturbation also induced plasmalemmal "ruffling". All VEG/PF-induced cytoskeletal changes were inhibited by preincubating endothelial cells with dexamethasone or anti-VEG/PF IgG antibody. CONCLUSION: The findings support a role for VEG/PF-induced cytoskeletal alterations in the pathophysiology of brain tumor angiogenesis and edemagenesis. These observations are likely to be directly linked to VEG/PF-induced endothelial cytosolic calcium flux. Insight into the mechanism of dexamethasone's clinical efficacy is also provided.

Expression of angiogenic factors and structural proteins in central nervous system vascular malformations.

Little is known of the molecular mechanisms mediating the genesis and subsequent biological behavior of central nervous system vascular malformations. The role of angiogenic and permeability-inducing factors in the pathogenesis of these lesions has not bee previously explored. In this study, we subject specimens from 12 cases of excised vascular malformation to a battery of immunostaining for vascular endothelial growth factor, basic fibroblast growth factor, and selected structural and matrix proteins. The lesions consisted of seven arteriovenous malformations (AVMs), including one angiographically occult AVM, one arterialized vein from a dural AVM, and five cavernous malformations (CMs). Vascular endothelial growth factor was expressed by all lesions and was localized predominantly in the subendothelial layer and in perivascular spaces. Four of seven AVMs and four of five CMs demonstrated faint basic fibroblast growth factor expression that was localized to the media of AVM vessels and the subendothelial layer and intercavernous matrix of CMs. This pattern of angiogenic factor immunostaining was correlated with the expression of structural and matrix proteins in the same lesions. Laminin was not expressed in any of the CMs, confirming previous reports from our laboratory. By contrast, fibronectin expression was more prominent in CMs than in AVMs. Collagen Type IV and alpha smooth muscle actin expression occurred in every lesion. We conclude that angiogenic growth factors are expressed in all types of vascular malformations of the central nervous system. The pattern of expression suggests diffuse activation of angiogenesis without specific relation to individual vessel types or recent clinical behavior. Defining the role of angiogenesis in vascular malformations might provide insight into their pathogenesis and suggest novel strategies for modification of their behavior.

Vascular endothelial growth/permeability factor expression in human glioma specimens: correlation with vasogenic brain edema and tumor-associated cysts.

Peritumoral vasogenic brain edema (PVBE) is a common accompaniment of malignant gliomas. It results from microvascular extravasation of plasma fluid and proteins through the interendothelial spaces. Tumor-associated cysts (TACs) are observed more commonly with benign gliomas that are not associated with PVBE. This study investigates the hypothesis that these morphologically distinct epiphenomena of microvascular extravasation are linked by a common pathophysiological mechanism involving vascular endothelial growth/permeability factor (VEG/PF), which has been implicated in vascular leak phenomena including ascites, malignant effusions, and brain edema. Furthermore, VEG/PF has been isolated from cultured glioma cells, and both VEG/PF protein and messenger RNA transcripts are expressed in brain tumor tissue. To further elucidate the relationship of VEG/PF to PVBE and TACs, the authors examined 34 pathological specimens for VEG/PF expression. Nineteen primary low-grade tumors, 11 primary high-grade tumors, and four gliosis controls were immunostained with a polyclonal anti-VEG/PF immunoglobulin G antibody. Magnetic resonance imaging was used to quantitate PVBE and to determine the presence of TACs and tumor enhancement. The study revealed that eight VEG/PF-negative specimens exhibited no significant edema, whereas 26 VEG/PF-positive tumors exhibited either significant PVBE or TACs. Notably, eight of nine benign TACs that were not associated with PVBE immunostained positive for VEG/PF. These data indicate a high degree of correlation between VEG/PF expression by gliomas and the occurrence of PVBE or TACs, irrespective of tumor grade, thus supporting VEG/PF's pivotal role as the common pathophysiological link between these processes.

Vascular permeability factor in brain metastases: correlation with vasogenic brain edema and tumor angiogenesis.

Metastatic brain tumors are almost always associated with vasogenic brain edema, which in turn plays a pivotal role in the evolution of neurological morbidity associated with these lesions. Attention has recently focused on a group of proteinaceous vascular permeability factors (VPF's) that are capable of inducing angiogenesis and promoting increased capillary permeability. To test the hypothesis that metastatic brain tumors expressing VPF's are associated with peritumoral cerebral edema, a rabbit polyclonal immunoglobulin (Ig) G anti-VPF was used to immunostain pathological specimens of metastatic cerebral tumors obtained from 22 patients who underwent surgery at Yale-New Haven Hospital. Magnetic resonance (MR) imaging was used to correlate VPF staining in tumor tissue with the occurrence of peritumoral brain edema. A histological study of the microvasculature was then conducted by immunostaining the specimens for endothelial cell factor VIII surface antigen, using two gliosis specimens as controls. Results revealed 21 of 22 tumors stained positively for VPF's; the negative-VPF tumor was a melanoma that exhibited no peritumoral edema. Twenty of 22 tumors had MR imaging-evident vasogenic edema. The presence and intensity of VPF immunostaining of microvascular features were noted and compared. Factor VIII staining demonstrated tumor vascularity to be most abundant in VPF-rich regions of tumor. The authors therefore report a high correlation between the presence of VPF's and the occurrence of peritumoral brain edema associated with cerebral metastases.

Prevention of "temporal hollowing" after fronto-orbital advancement for craniosynostosis.

Depression of profile in the temporal region is commonly seen after orbital rim advancement procedures. A newly developed temporalis musculoosseous flap has been designed with the intent to prevent this postoperative occurrence.

Massive orbital teratoma in the newborn.

Teratomas are rare germ cell tumors that comprise approximately 1% of orbital tumors in childhood. Review of the world literature revealed only 51 well-documented patients with true congenital orbital teratomas. We present a newborn girl with a massive orbital teratoma that caused significant orbital enlargement with inferior and lateral displacement of the zygoma and a thinning of the orbital roof. The ipsilateral maxilla and palate were depressed inferiorly. No bony invasion was seen despite its massive size. A craniofacial approach was used to safely and completely extirpate this tumor. Histological sections demonstrated derivatives of all three germ cell layers. Recommendations for definitive treatment and a review of the literature are presented.

The genesis of peritumoral vasogenic brain edema and tumor cysts: a hypothetical role for tumor-derived vascular permeability factor.

Cerebral edema and fluid-filled cysts are common accompaniments of brain tumors. They contribute to the mass effect imposed by the primary tumor and are often responsible for a patient's signs and symptoms. Cerebral edema significantly increases the morbidity associated with tumor biopsy, excision, radiation therapy, and chemotherapy. Both edema and cyst formation are thought to result from a deficiency in the blood-brain barrier, with consequent extravasation of water, electrolytes, and plasma proteins from altered tumor microvessels. The resultant expansion of the cerebral interstitial space contributes to the elevated intracranial pressure observed with brain tumors. Departure from the typical blood-brain barrier microvascular architecture may only partially explain the occurrence of edema and tumor cyst formation. Biochemical mediators have also been implicated in vascular extravasation. Vascular permeability factor or vascular endothelial growth factor (VPF/VEGF) is a protein that has recently been isolated from a variety of tumors including human brain tumors. VPFb is an extraordinarily potent inducer of both microvascular extravasation (edemagenesis) and the formation of new blood vessels (angiogenesis). Its role in tumor growth and progression would therefore appear pivotal. Herein, the author presents an updated account of the investigation of VPF. Historical and clinical perspectives of the study and treatment of tumor associated edema are provided. The efficacy of high-dose dexamethasone in the treatment of neoplastic brain edema is discussed. A hypothetical role for VPF in edemagenesis is presented and discussed. It is hoped that an expanded understanding of the mechanisms responsible for the genesis of edema will ultimately facilitate therapeutic intervention.

Clivus chordoma: a report of 12 recent cases and review of the literature.

Twelve patients with histologically confirmed clivus chordoma were treated at the Johns Hopkins Hospital between 1971 and 1989. Eight of the patients were men and four were women. The mean age at first operation was 51 years (range, 10 to 80). The most common presenting symptoms were headache, diplopia, dysphagia and dysarthria, and facial sensory changes. Computed tomography, with and without contrast enhancement, proved adequate for tumor identification and localization. Magnetic resonance imaging and angiography were occasionally employed to localize the tumors further and to define tumor vascular supply and proximity to vascular structures. Twenty-two resections were performed in 11 patients, and another patient underwent biopsy only. Seven were also treated with radiation therapy. Tumors recurred in eight patients, six of whom underwent further operations. The mean time to first recurrence was 22 months (range 8 to 36 months). Six of the patients are still alive, with a mean follow-up of 31 months (range, 3 to 89 months) from first surgical resection. The mean survival time from first treatment was 31 months (range, 4 to 62 months) among those patients who died. There was no operative mortality. The 5-year cumulative survival rate was 20%. Six patients with long follow-up have had fair to good results, being free of recurrences for at least a year. However, none of the patients returned to their premorbid baseline of activities. Five of the patients had tumors with the histologic diagnosis of chondroid chordoma. Three of these patients are still alive. The mean age at first treatment was 44 (compared with 62 for typical chordomas). The mean time from symptoms to diagnosis was 29 months (typical chordomas, 18 months). The mean length of survival and time to tumor recurrence were not significantly different between chondroid and typical chordomas.

Tratamiento de las neoplasias cervicales intraepiteliales de alto grado con interferoon alfa leucocitario por vía intralesional / Treatment of neoplasm cervical with IFN leukocyte Alfa Through intralesional via

Se analiza el material de 10 pacientes tratados con IFN alfa leucocitario por vía peri e intralesional. Sus edades oscilan entre 21 y 38 años (promedio 26,6 años). En 3 casos el diagnóstico histopatológico fue de CIN II a III y en 7 casos fue de CIN III. La respuesta al tratamiento fue evaluada por colposcopia, citología e histología. Las parejas masculinas se controlaron con penoscopias. El tiempo promedio de seguimiento fue de 19,3 meses con un rango de 12 a 30 meses. Del total, nueve pacientes prestaron remisión completa histológica d esus displasias. Una paciente no respondió a la terapia. Al año del tratamiento ninguna de las pacientes que completaron este control presentaron recidivas. Las recurrencias histológicas observadas fueron hasta el momento a CIN I. Cuatro de las cinco pacientes con condilomas detectados en la penoscopia remitieron luego del tratamiento. En función de estos resultados se podría considerar el tratamiento con IFN alfa una opción terapêutica válida

Tratamiento de las neoplasias cervicales intraepiteliales de alto grado con interferoon alfa leucocitario por vía intralesional / Treatment of neoplasm cervical with IFN leukocyte Alfa Through intralesional via

Se analiza el material de 10 pacientes tratados con IFN alfa leucocitario por vía peri e intralesional. Sus edades oscilan entre 21 y 38 años (promedio 26,6 años). En 3 casos el diagnóstico histopatológico fue de CIN II a III y en 7 casos fue de CIN III. La respuesta al tratamiento fue evaluada por colposcopia, citología e histología. Las parejas masculinas se controlaron con penoscopias. El tiempo promedio de seguimiento fue de 19,3 meses con un rango de 12 a 30 meses. Del total, nueve pacientes prestaron remisión completa histológica d esus displasias. Una paciente no respondió a la terapia. Al año del tratamiento ninguna de las pacientes que completaron este control presentaron recidivas. Las recurrencias histológicas observadas fueron hasta el momento a CIN I. Cuatro de las cinco pacientes con condilomas detectados en la penoscopia remitieron luego del tratamiento. En función de estos resultados se podría considerar el tratamiento con IFN alfa una opción terapÛutica válida (AU)

Cytosolic calcium changes in endothelial cells induced by a protein product of human gliomas containing vascular permeability factor activity.

A vascular permeability factor (VPF) derived from serum-free conditioned medium of cultured human malignant gliomas (HG-VPF) has been described previously. The rapid kinetics of HG-VPF activity in an in vivo assay of vascular permeability suggests a direct action upon the vascular endothelial cell. To determine whether HG-VPF was capable of inducing a physiologically significant alteration in isolated endothelial cells, cytosolic calcium [Ca++]i was measured in vitro in these cells before and after their exposure to media containing this substance. This was accomplished by preloading cultured endothelial cells with a fluorescent intracellular Ca++ probe fura-2/AM. It was found that HG-VPF induced a rapid and transient elevation of [Ca++]i in normal endothelial cells derived from human umbilical vein, bovine adrenal medulla, bovine pulmonary artery, and rat brain. This effect was inhibited by chelating extracellular calcium [Ca++]e with ethyleneglycol-bis (beta-aminoethylether)-N,N'-tetra-acetic acid (EGTA), indicating that the HG-VPF-induced response resulted from the influx of extracellular calcium. The addition of cations that act as nonspecific calcium channel blockers (Li+, Co++, Mn++, La ) completely inhibited VPF activity, further supporting the role of [Ca++]e influx. The HG-VPF activity was not, however, blocked by verapamil, a calcium antagonist that appears to be specific for voltage-gated calcium channels. Furthermore, exposure of endothelial cells to 120 mM [K+]e did not result in a calcium transient. Coincubation of endothelial cells with dexamethasone inhibited HG-VPF-induced rises in [Ca++]i, while having no effect upon cyclic nucleotide-induced changes in calcium. The present studies indicate that vascular extravasation induced by human glioma-derived VPF may be mediated by a direct action upon vascular endothelial cells. Furthermore, the observed dexamethasone-induced inhibition of this process suggests a specific cellular action for corticosteroids. This, together with previous observations that dexamethasone suppresses both the production of VPF by tumor cells in vitro and its permeability-inducing activity in vivo, may explain the efficacy of glucocorticoids in the treatment of neoplastic vasogenic brain edema. Finally, studies with a polycationic peptide (protamine) known to induce blood-brain barrier disruption in vivo revealed similar effects upon endothelial cytosolic calcium levels. As HG-VPF is a positively charged macromolecule, a common interaction between these substances and the negatively charged endothelial cell surface in the induction of permeability is suggested. Nonspecific cross-linking of charged groups of the endothelial glycocalyx and specific HG-VPF receptor binding are both valid mechanisms of HG-VPF-mediated calcium changes. Their potential relevance in the setting of microvascular permeability is discussed.

Reversible acute and subacute myelopathy in patients with dural arteriovenous fistulas. Foix-Alajouanine syndrome reconsidered.

Acute or subacute neurological deterioration without evidence of hemorrhage in a patient with a spinal arteriovenous (AV) malformation has been referred to as "Foix-Alajouanine syndrome." This clinical entity has been considered to be the result of progressive vascular thrombosis resulting in a necrotic myelopathy; it has therefore been thought to be largely irreversible and hence untreatable. The authors report five patients with dural AV fistulas who presented in this manner, and who improved substantially after embolic and surgical therapy. The outcome of these patients indicates that acute and subacute progression of myelopathy in cases of spinal dural AV fistulas may be caused by venous congestion and not necessarily by thrombosis. Therefore, a clinical diagnosis of Foix-Alajouanine syndrome is of little practical use, as spinal cord dysfunction from venous congestion is a potentially reversible process whereas thrombotic infarction is not. This diagnosis may result in suboptimal management. The recognition of nonhemorrhagic acute or subacute myelopathy as a complication of a spinal dural AV fistula is important since what appears to be irreversible cord injury is often treatable by standard surgical techniques.

Measurement of intracranial tissue volume using computed tomographic images and a personal computer.

A software package called MacMeasure was developed previously to measure the size of intracellular structures by means of photomicrographs. We have expanded the application of this program to computed tomographic (CT) images. Using three objects of irregular shape and unequal size (phantoms), we compared volumetric determinations made with a CT mainframe computer and a widely available personal computer. The phantom objects were scanned in a GE CT/T 9800 scanner with serial, nonoverlapping slices 3.0 mm in thickness. The image data were first measured directly from the magnetic archive tape with the CT control terminal. Hard copies of the CT scans were then measured with a Macintosh SE computer and a digitizing tablet with a crosshair cursor driven by the MacMeasure software package. A third method of measuring volume was by tracing individual CT images onto paper (hard copies). The tracings were then cut out, weighed, and converted to surface area by dividing the weights by a weight/surface area standard (26.37 mg = 25 cm2) calibrated to the CT image scale (5.0 cm). The total surface area value was then converted to volume by multiplying by a single CT slice thickness (0.3 cm). Finally, the phantom objects were placed in water-filled graduated cylinders to determine their volume by fluid displacement. The technique using MacMeasure and the personal computer provides an accurate means of determining surface area and volumes using hard copies of CT images. It avoids occupying costly CT computer time and is the most rapid method of volume measurement of the three techniques tested (CT mainframe = 6.0 hours, trace/weigh = 3.5 hours, and PC = 1.25 hours).(ABSTRACT TRUNCATED AT 250 WORDS)