Levels of soluble vascular endothelial growth factor (VEGF) receptor 1 in astrocytic tumors and its relation to malignancy, vascularity, and VEGF-A.

PURPOSE: Vascular endothelial growth factor (VEGF)-A isa key mediator of angiogenesis in malignant gliomas. Soluble VEGF receptor 1 (sVEGFR-1) can complex VEGF-A and reduce its bioavailability. In several animal models sVEGFR-1 inhibited angiogenesis and tumor growth. We analyzed the levels of endogenous sVEGFR-1 in gliomas of different malignancy grades in relation to tumor vascularity and VEGF-A. EXPERIMENTAL DESIGN: The concentration of sVEGFR-1 was determined by ELISA in 104 gliomas and normal brain. Levels of sVEGFR-1 were compared with malignancy grade, microvessel density, and VEGF-A concentration. Effects of sVEGFR-1 on glioma extract-induced endothelial cell chemotaxis were analyzed in vitro. RESULTS: The concentration of sVEGFR-1 correlated with the malignancy grade and was 12-fold higher in glioblastomas than in diffuse astrocytomas (P < 0.001), with intermediate levels for anaplastic astrocytomas. VEGF-A levels were 30-fold higher (P < 0.001) in glioblastomas than in diffuse astrocytomas. The sVEGFR-1:VEGF-A ratio was 0.27 in glioblastomas and 0.70 in diffuse astrocytomas. Both sVEGFR-1 and VEGF-A correlated with microvessel density (P < 0.001) and with each other (P < 0.001); sVEGFR-1 and VEGF-A also correlated with each other when only glioblastomas were analyzed (P = 0.001). In vitro, recombinant sVEGFR-1 inhibited endothelial cell chemotaxis induced by tumor extracts. CONCLUSIONS: Although absolute levels of sVEGFR-1 are increased in the more malignant gliomas, the sVEGFR-1:VEGF-A ratio is decreased 2.6-fold in glioblastomas compared with diffuse astrocytomas, suggesting that the ensuing increased bioavailability of VEGF-A favors angiogenesis. The inhibition of tumor extract-induced endothelial chemotaxis by sVEGFR-1 suggests that sVEGFR-1 could be useful as an angiogenesis inhibitor in the specific context of human gliomas.     

Frakturen bei Patienten mit Meningomyelozele

Zusammenfassung Anhand von 3 Fallbeispielen aus der Spina-bifida-Ambulanz der Klinik für Kinder und Jugendliche der Universit?t Erlangen wird über die Problematik von Frakturen bei Patienten mit Meningomyelozele sowie deren Therapiekonzept berichtet. In übereinstimmung mit Literaturberichten zeigen die Kasuistiken, da? schwere Allgemeinreaktionen, lokale und systemische Entzündungsparameter und variable radiologische Befunde mit h?ufig ausgedehnter reaktiver Kallusbildung die Diagnosestellung von Frakturen bei Patienten mit Meningomyelozele, die nicht selten schmerzlos und ohne erinnerliches Trauma verlaufen, erheblich erschweren k?nnen. Differentialdiagnostisch kommen Osteomyelitis, maligne Knochentumoren und aneurysmatische Knochenzysten in Frage. Diskussion: Statische Belastung durch Geh-/ Stehtraining sowie die Verkürzung von Immobilisationsphasen stellen wichtige Faktoren in der Prophylaxe von Frakturen bei Meningomyelozyelepatienten dar. Das Therapiekonzept von Frakturen bei unserer Patientengruppe weist wesentliche Unterschiede zu den allgemeinen unfallchirurgischen und orthop?dischen Richtlinien auf.      

Intravenous Leiomyomatosis of the Uterus

Three cases of intravenous leiomyomatosis (IVL) of the uterus, a rare benign smooth-muscle tumor, are described. A preoperative diagnosis of IVL was not made in any of the patients, all of which presented with a pelvic mass with the presumptive diagnosis of leiomyoma. Surgical exploration confirmed the presence of uterine mass and two of the three cases showed extra-uterine extension into the ovarian or uterine veins. Histological examination demonstrated a fascicular pattern of bland spindle-shaped smooth-muscle cells, which extended to veins inside the myometrium or to extrauterine veins. This was confirmed by immunohistochemical stain for desmin and factor VIII. Despite their histological benignity, these lesions have a tendency to metastasize and are closely related to the conditions called “benign metastasizing leiomyoma” and “intracaval mass and cardiac extension”. The primary treatment of IVL is hysterectomy and excision of any extrauterine tumor, when technically feasible. Anti-estrogenic therapy has been suggested as potentially useful in controlling of unresectable tumor. According to the literature, the follow-up must be long and periodic postoperative ultrasonic or magnetic nuclear resonance imaging studies may be useful in detecting growth of residual intravascular tumor.     

Effects of acute tryptophan depletion on negative symptoms and smoking topography in nicotine-dependent schizophrenics and nonpsychiatric controls.

We studied the effect of acute tryptophan depletion (ATD), which transiently reduces brain serotonin, on negative symptoms and cigarette smoking topography in schizophrenic smokers. Nicotine-dependent schizophrenics (n=11) and nonpsychiatric controls (n=8) were examined after ingesting comparable mixtures that do and do not deplete plasma tryptophan. Tryptophan-depleting and placebo mixtures were administered double-blind and in counterbalanced order. Conditions were separated by a 1-week interval. Psychopathologic symptoms (negative symptoms, depression) and smoking topography (time to first puff, number of puffs per cigarette, puff duration, interpuff interval, cigarette duration, and percentage of cigarette smoked) were measured before ingestion and again beginning 5 h after each mixture, corresponding to the time of maximal tryptophan depletion. Analyses were conducted using repeated measures analyses of variance (psychopathologic symptoms) and analyses of covariance (smoking topography) controlling for cigarette length. We found that ATD influenced smoking topography in both schizophrenics and nonpsychiatric controls in a manner suggestive of increased desire to smoke. Schizophrenics exhibited increased puff duration and decreased cigarette duration. Controls displayed increased puff duration. ATD did not produce changes in negative symptoms or depression. Compromising brain serotonin via ATD appears to intensify smoking behavior in nicotine-dependent individuals directly, rather than indirectly through changes in either mood or psychopathologic symptoms.     

Acute cardiopulmonary alterations induced by fine particulate matter of S?o Paulo, Brazil.

The mechanisms involved in the association between air pollution and increased cardiovascular morbidity are not fully understood. The objective of this study was to test the hypothesis that fine particulate matter (PM(2.5)) induces systemic inflammation and vasoconstriction of small arteries in the lung and heart of rats. Thirty-eight healthy Wistar rats were anesthetized, intubated, and submitted to the instillation of 1 ml of distilled water diluted in the following solution: blank filter, 100 microg and 500 microg of PM(2.5). PM(2.5) was collected in glass fiber filters with a high-volume sampler. The animals were sacrificed 24 h after instillation when blood, heart, and lung samples were collected for morphological and wet-to-dry weight ratio analysis. PM(2.5) consisted of the following elements: sulphur, arsenic, bromine, chlorine, cobalt, iron, lanthanum, manganese, antimony, scandium, and thorium. Total reticulocytes significantly increased at both PM(2.5) doses (p < 0.05) while hematocrit levels increased in the 500 microg group (p < 0.05). Quantification of segmented neutrophils and fibrinogen levels showed a significant decrease, while lymphocytes counting increased with 100 microg of PM(2.5) (p < 0.05). A significant dose-dependent decrease of intra-acinar pulmonary arteriole lumen/wall ratio (L/W) was observed in PM groups (p < 0.001). Peribronchiolar arterioles L/W showed a significant decrease in the 500 microg group (p < 0.001). A significant increase in heart wet-to-dry weight ratio was observed in the 500 microg group (p < 0.001). In conclusion, fine environment particles in the city of S?o Paulo promote pulmonary and cardiac histological alterations. Pulmonary vasculature was markedly affected by particle instillation, resulting in significant vasoconstriction in healthy rats.     

The use of the female condom by women in Brazil participating in HIV prevention education sessions.

OBJECTIVES: To study HIV-positive women and women at risk of becoming infected with HIV who attended HIV prevention education group sessions at a university hospital in Brazil and to compare the use of the female condom and the male condom by these two groups of women. METHODS: The study subjects were 165 women participating in HIV prevention education group sessions at the Medical School Hospital of Ribeir?o Preto of the University of S?o Paulo, in the city of Ribeir?o Preto, S?o Paulo, Brazil. Women could be enrolled in the study from August 2000 to June 2001, and the follow-up observation time period was from August 2000 to July 2001. Male condoms and female condoms were freely distributed to all the participants at the end of each educational session and also at the end of each follow-up visit that the participants made. Each woman took part in an initial interview and was asked to return monthly. At each follow-up visit an additional short interview was carried out in order to investigate use of the male condom and of the female condom. Variables that were examined for the study included age, education, ethnic group, marital or relationship status, number of children, the women's use of male condoms and female condoms, commercial sex (whether the women had ever had sex in exchange for money, gifts, or favors), and previous knowledge of the female condom. RESULTS: The 165 women studied fell into the following three categories: 132 of them (80.0%) were HIV-positive, 26 of them (15.8%) had a sexually transmitted disease (STD) other than HIV and did not have an HIV-positive partner, and 7 of them (4.2%) had an HIV-positive partner but did not have HIV or any other STD. The women ranged in age from 15 to 64 years, with a mean of 30.3 years. Of the women in the study, 69.7% of them were married or were cohabitating, and 90.9% of them had a sexual partner. Just over two-thirds of the women had seven years of formal schooling or less. Out of 163 women, a total of 31 of them (19.0%) had never used the male condom with a partner, and 49 of the 163 (30.1%) had not used a male condom at the time of the last sexual intercourse. Out of the 165 women, 74 of them (44.8%) returned for at least one follow-up visit. Of these 74 women, 58 of them (78.3%) reported using the female condom between the initial interview and the first follow-up visit. The majority of the 74 women who returned for a visit liked using the female condom, and the women reported that their partners also generally accepted the female condom. In comparison to women at risk of HIV, HIV-positive women were more likely to have used the male condom with a partner before the initial interview. Women who continued returning over a longer follow-up period were more likely to have used the female condom at the time of the last sexual intercourse. No association was found between female condom use at the time of last sexual intercourse and the woman's HIV infection status. CONCLUSIONS: In comparison to the women at risk of HIV, the HIV-positive women in our study were more likely to use male condoms with their partners, to return for follow-up visits, and to have a longer follow-up period. The acceptance of the female condom among the HIV-positive women in this study, as reported at their first follow-up visit, appears to be similar to the acceptance of the female condom among women in general in Brazil.     

Computer based sleep recording and analysis

Sleep analysis is based on polysomnography. Modern polysomnographic systems are computer based. Visual and automatic analysis of sleep and respiration is supported by most computer based systems. Four functions can be distinguished in computer based polysomnography: recording, documentation during the recording, automatic and visual analysis and report generation. This review compiles the minimal requirements for digital sleep recording, documentation, analysis and reporting. The basic principles of automatic sleep analysis are reported. The requirements and the basic principles for the analysis of non-electroencephalography (EEG) signals, such as respiration, snoring, oxygen saturation, electrocardiography (ECG) and options are reported. New developments in sleep EEG processing are discussed to enlighten how computer based sleep analysis can add quantative parameters to the rules for visual sleep staging established by Rechtschaffen and Kales 30 years ago. This helps to extend our understanding of sleep.     

The emergency treatment of aneurysms of the supra-aortic trunks and of the internal carotid

In the last 10 years, four patients with aneurysms of the supraaortic trunks and the internal carotid artery have been operated in emergency at Department of Vascular Surgery of University of Bari. The first case was a mycotic aneurysm of the carotid bifurcation, the second an aneurysm of internal carotid artery interesting the retropharynx, the third a post-operatory pseudoaneurysm of common carotid in a patient affected by Takayasu's disease and the last an atherosclerotic aneurysm of the innominate artery. Clinical picture suggested an immediate surgical treatment in all patients. Different procedure were used depending on size and localization of each lesion. Results in all cases have been satisfactory. The aneurysms of supraaortic trunks and of internal carotid artery are very rare; therefore when clinical picture is dramatic or quickly worsening, emergency treatment is mandatory in order to reduce mortality risk and minimize complications.     

Inflammation induced by Bothrops asper venom: release of proinflammatory cytokines and eicosanoids, and role of adhesion molecules in leukocyte infiltration.

Bothrops asper venom (BaV) causes systemic and local effects characterized by an acute inflammatory reaction with accumulation of leukocytes and release of endogenous mediators. In this study, the effects of BaV on the release of the cytokines IL-1, IL-6 and TNF-alpha and the eicosanoids LTB4 and TXA2 in the peritoneal cavity of mice were analyzed. We also investigated the participation of beta2 integrin chain, l-selectin, LFA-1, ICAM-1 and PECAM-1 adhesion molecules in the BaV-induced leukocyte accumulation. Levels of proinflammatory cytokines IL-6 and TNF-alpha, as well as eicosanoids LTB4 and TXA2 were significantly increased after BaV injection (250 microg/kg), whereas no increment in IL-1 was observed. Anti-mouse l-selectin, LFA-1, ICAM-1, PECAM-1 and beta2 integrin chain monoclonal antibodies resulted in a reduction of neutrophil accumulation induced by BaV injection compared with isotype-matched control injected animals. These data suggest that BaV is able to induce the activation of leukocytes and endothelium to express adhesion molecules involved in the recruitment of neutrophils into the inflammed site. Furthermore, these results showed that BaV induces the release of cytokines and eicosanoids in the local of the venom injection; these inflammatory mediators may be important for the initiation and amplification of the inflammatory reaction characteristic from Bothrops sp envenomation.     

Abstinence from cocaine self-administration heightens neural encoding of goal-directed behaviors in the accumbens.

Cocaine addiction in humans is characterized by cycles of abstinence from drug-taking and relapse. Here, electrophysiological recording procedures were used to determine whether nucleus accumbens (Acb) neuronal firing properties are altered following interruption and resumption of cocaine self-administration. Rats (n = 12) were trained to self-administer cocaine (2 h daily sessions) then divided into two groups. Acb activity was recorded for Group 1 (controls) during two additional self-administration sessions completed over the next 2 days (test sessions 1 and 2). Acb activity was recorded for Group 2 (1-month) during one self-administration session completed the next day (test 1), and during a second self-administration session 1 month later (test 2). As in prior reports, a subset of Acb neurons exhibited patterned discharges (short duration and/or long-term cyclic alterations, termed 'phasically active') relative to cocaine-reinforced responding during test session 1. Remarkably, the percentage of phasically active cells dramatically increased (nearly two-fold) following 1-month abstinence, in the core but not the shell of the Acb. Likewise, the strength of the neural correlates (determined via signal-to-baseline ratios) also increased as a function of abstinence. Extinction experiments in another set of rats (n = 12) revealed an increased motivational state for the drug following abstinence. The results show that abstinence from cocaine self-administration causes a dramatic increase in the number and strength of Acb neurons that encode cocaine-related information, thus representing the first neurophysiological correlate of heightened activation of the 'brain reward system' following abstinence and resumption (relapse) of cocaine consumption.