Brain edema in meningiomas is associated with increased vascular endothelial growth factor expression

OBJECTIVE: Vascular permeability factor/vascular endothelial growth factor (VPF/VEGF), an endothelial cell-specific cytokine, induces proliferation of endothelial cells and increases vascular permeability dramatically. All gliomas secrete significant amounts of VEGF, whereas meningiomas are variable in expression. Thus, we sought to determine whether the extent of VPF/VEGF expression in meningiomas correlated with differences in brain edema associated with these tumors. METHODS: Meningioma tissue samples from 37 patients (15 men, average age 65 +/- 13 yr; 22 women, average age 60 +/- 10 yr) who underwent surgery at or were referred to the University of Alabama Hospital were examined retrospectively for the extent of expression of immunoreactive VPF/VEGF. Additionally, peritumoral edema was assessed on a blinded basis radiographically from preoperative magnetic resonance imaging scans. Selected specimens were examined by in situ hybridization to document the source of VPF/VEGF. RESULTS: The predominant meningioma subclassifications were transitional (57%) or meningothelial (27%) subtypes. VPF/VEGF immunoreactivity ranged from 0 to 3.5, with a median value of 2 on a subjective 5-point scale; magnetic resonance imaging-assessed edema ranged in extent from 0 to 4 (subjective 5-point scale), with a median value of 2.5. The correlation of determination (R2) of magnetic resonance imaging-assessed tumor edema rating and VPF/VEGF staining intensity rating was 0.6087 (r = 0.78; P = 0.0001). In situ hybridization localized VPF/VEGF messenger ribonucleic acid in meningioma cells and not in normal parenchymal brain cells. CONCLUSION: These data suggest that meningioma-associated edema may be a result of the capacity of meningioma cells to produce VPF/VEGF locally, leading to increased tumor neovascularization and enhanced vascular permeability.     

Delayed nonmatch-to-sample performance in HIV-seropositive and HIV-seronegative polydrug abusers.

Working memory (WM) deficits are common in HIV-seropositive (HIV+) individuals and can be amplified by manipulating a variety of task parameters, such as increasing memory load or information complexity. The authors investigated the role of timing in HIV-associated WM defects by varying the amount of time required to maintain information online while holding memory load and information complexity constant. The authors studied 50 HIV+ and 35 HIV-seronegative (HIV-) polydrug abusers abstinent at testing and well-matched on demographic variables. The HIV- group outperformed the HIV+ group across all stimulus-response time delays. HIV-associated WM defects are not critically dependent on the amount of time stimulus representations must be maintained and might be attributed to impaired encoding or retrieval of stimulus representations. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

In vitro and in vivo gene delivery mediated by a synthetic polycationic amino polymer

The r?le of chemotherapy in the treatment of operable soft tissue sarcomas is still debatable. In high-grade tumors, randomized trials using adjuvant chemotherapy have resulted in controversial results. A recent meta-analysis showed a higher median disease-free survival in groups with chemotherapy compared to controls. Doxorubicin, ifosfamide and dacarbazine are the majors drugs. Their combination in adjuvant treatment is currently being investigated. Neoadjuvant chemotherapy has allowed conservative surgery in initially unoperable tumors, but its role in primarily operable tumors remains to be defined.     

Corpuscles of Stannius and stanniocalcin-like immunoreactivity in the white sucker (Catostomus commersoni): evidence for a new cell-type

BACKGROUND: A recent study found that a higher-perfusate hematocrit was associated with improved neurologic recovery after deep hypothermic circulatory arrest. The current study examined the relative contributions of oxygen delivery and colloid oncotic pressure to this result, as well as the efficacy of different colloidal agents and modified ultrafiltration. METHODS: Twenty-six piglets were randomized into five groups (n = 5 or 6 animals per group): control group 1--blood and crystalloid prime, hematocrit of 20%; group 2--blood and hetastarch prime, hematocrit of 20%; group 3--blood and pentafraction prime, hematocrit of 20%; group 4--blood and crystalloid prime with 10 minutes of modified ultrafiltration; group 5--whole blood prime, hematocrit of 30%. All groups underwent 60 minutes of deep hypothermic circulatory arrest at 15 degrees C. RESULTS: Groups 2 and 3 showed less body weight gain (analysis of variance, p = 0.001; group 2 versus group 1, p = 0.0009; group 3 versus group 1, p = 0.0009) and body water content after cardiopulmonary bypass (analysis of variance, p = 0.001; group 2 versus group 1, p = 0.003; group 3 versus group 1, p = 0.013). Group 5 showed more rapid recovery of phosphocreatine and intracellular acidosis, as measured by magnetic resonance spectroscopy, during rewarming than group 1 did (phosphocreatine, p = 0.0329; intracellular acidosis, p = 0.0462). Group 3 also showed accelerated recovery of intracellular acidosis (p = 0.0411). Cytochrome a,a3 recovery, determined by near-infrared spectroscopy, was significantly better in group 5 than in group 1 and worse in group 2 than in group 1 after rewarming. The neurologic deficit score and overall performance category score were best in group 5 (neurologic deficit score, p = 0.012; overall performance category score, p = 0.046) on the first postoperative day. Group 3 also had a better overall performance category score than group 1 did (p = 0.0068). Only group 1 and 2 animals showed histologic damage. CONCLUSIONS: Both higher hematocrit and higher colloid oncotic pressure with pentafraction improve cerebral recovery after deep hypothermic circulatory arrest. The higher hematocrit improves cerebral oxygen delivery but does not reduce total body edema. Modified ultrafiltration after cardiopulmonary bypass is less effective than having a higher initial prime hematocrit or colloid oncotic pressure.     

Improved survival in stage III melanoma patients with GM2 antibodies: a randomized trial of adjuvant vaccination with GM2 ganglioside

PURPOSE: To perform a double-blind randomized trial with American Joint Commission on Cancer (AJCC) stage III melanoma patients for the following reasons: (1) to confirm our previous finding that patients with antibodies against the melanoma differentiation antigen GM2 have an improved prognosis, and (2) to demonstrate clinical benefit from GM2 antibody induction. PATIENTS AND METHODS: One hundred twenty-two patients with AJCC stage III melanoma who were free of disease after surgery were randomized: 58 to receive treatment with the GM2/BCG vaccine, and 64 to receive treatment with bacille Calmette-Guèrin (BCG) alone. All patients were pretreated with low-dose cyclophosphamide (Cy). RESULTS: GM2 antibody was detected in 50 of 58 patients treated with GM2/BCG and seven of 64 patients treated with BCG alone. With a minimum follow-up period of 51 months, there was a highly significant increase in the disease-free interval (P = .004) and a 17% increase in overall survival (P = .02) in these 57 antibody-positive patients, confirming our earlier experience. Exclusion of all patients with preexisting GM2 antibodies (one in the GM2/BCG group and five in the BCG group) from statistical analysis resulted in a 23% increase in disease-free interval (P = .02) and a 14% increase in overall survival (P = .15) at 51 months for patients treated with the GM2/BCG vaccine. However, when all patients in the two treatment groups were compared as randomized, these increases were 18% for disease-free interval and 11% for survival in the GM2/BCG treatment group, with neither result showing statistical significance. CONCLUSION: (1) Vaccination with GM2/BCG induced immunoglobulin M (IgM) antibodies in most patients. (2) GM2 antibody production was associated with a prolonged disease-free interval and survival. (3) Comparison of the two arms of this trial as randomized fails to show a statistically significant improvement in disease-free interval or survival for patients treated with GM2/BCG vaccines.     

Changes in natural killer cell activity and prostaglandin E2 levels during the progression of diethylnitrosamine-induced hepatocarcinogenesis in Fischer 344 rats

The sequential changes of natural killer cell (NK) activity and prostaglandin E2 (PGE2) during hepatocarcinogenesis induced by diethylnitrosamine (DEN) in male Fischer 344 rats were investigated. DEN at a concentration of 40 ppm was administered in drinking water for 10 weeks. At weeks 5, 10, 20 and 30, rats were autopsied and the development of glutathione S-transferase placental form positive foci (GST-P+ foci) at weeks 5 and 10 and hepatocellular tumors at weeks 20 and 30 were examined. The labeling index of bromodeoxyuridine (BrdU) an indicator of DNA synthesis, was also sequentially checked. GST-P+ foci were found to increase with age. Hepatocellular nodules increased until week 20, but by week 30 when the incidence of hepatocellular carcinoma was 100%, the incidence of nodules had decreased. BrdU positive cells also increased with age, and by week 30 when the incidence of hepatocellular carcinoma was 100%, the number of BrdU-positive cells had decreased. NK cell activity increased until week 10, but at week 20, was less than in the untreated control group. The level of PGE2 increased until week 5, but at week 10, levels were not significantly different from those seen in the untreated control group. On the basis of these results, we concluded that NK activity is closely related to the progression of hepatocarcinogenesis, but PGE2 levels show no significant change.     

Problems in managing patients with long QT syndrome and implantable cardioverter defibrillators: a report of two cases

Implantable cardioverter-defibrillators (ICDs) have been a successful adjunct to the management of arrhythmias in patients with Long QT syndrome (LQTS). In two patients, interactions between LQTS and the ICD were diagnosed and corrected. Oversensing of T waves was confirmed in the first, while in the second, the arrhythmia disappeared when T wave abnormalities improved after cessation of H2 blocker therapy. In patients with LQTS and an ICD, T wave oversensing should be considered. Interventions that may have an adverse effect on repolarization should be avoided.     

Combined treatment of acute EAE in Lewis rats with TNF-binding protein and interleukin-1 receptor antagonist

Experimental autoimmune encephalomyelitis (EAE) is a term given to describe a collection of animal models representing the human disease multiple sclerosis (MS). Although not fully understood, the involvement of cytokines and the immune system in either EAE or human MS is well established. Past efforts have shown that inhibition of proinflammatory cytokines tumor necrosis factor (TNF-alpha) or interleukin-1 (IL-1) result in amelioration of acute EAE in Lewis rats. The present study examined this model for the effect of concomitant inhibition of both TNF-alpha and IL-1, which resulted in a modest but significant therapeutic effect that was superior to inhibition of either single agent alone with respect to four of the five variables used to follow the progression of disease in this model, i.e., clinical severity, frequency of disease, loss of body weight, and day of onset. These results are in accordance with the idea that combination treatments are likely to prove superior to single agent therapy in the treatment of autoimmune inflammatory disease.     

Infraclavicular brachial plexus block: parasagittal anatomy important to the coracoid technique

OBJECTIVE: This study's objective was to determine whether the concentrations of beta-human chorionic gonadotropin in the secretions of the cervix and vagina could be used to predict preterm delivery in a group of women at high risk for this complication. STUDY DESIGN: Women attending a prematurity prevention clinic at an inner-city hospital July 1, 1996-October 1, 1997, were invited to participate. From those who consented, secretions from the cervix and posterior vaginal fornix were sampled every 2 weeks until delivery, beginning at 24 weeks' gestation. Concentrations of beta-human chorionic gonadotropin were measured with a commercially available enzyme-linked immunosorbent assay. Providers of obstetric care were blinded to the results. Levels of beta-human chorionic gonadotropin in those who were delivered before 34 weeks' gestation and those who were delivered at term were compared. A value >50 mIU/mL was considered elevated. This cutoff value was determined according to beta-human chorionic gonadotropin values obtained during pregnancies that were delivered at term. RESULTS: Of the 146 women asked to participate, 77 consented. There was no difference between participants and nonparticipants with respect to age, race, indication for enrollment in the clinic, gestational age at delivery, or parity. Of the 77 participants, 24 (31%) were delivered before 37 weeks' gestation and 12 (16%) were delivered before 34 weeks' gestation. A single beta-human chorionic gonadotropin value >50 mIU/mL obtained between 24 and 28 weeks' gestation was associated with a significant increase in the incidence of delivery before 34 weeks' gestation (P = .03). This cutoff value had sensitivity, specificity, and positive and negative predictive values for predicting delivery before 34 weeks' gestation of 50%, 87%, 33%, and 93%, respectively. CONCLUSION: These data suggest that the concentration of beta-human chorionic gonadotropin in cervicovaginal secretions may be a useful predictor of preterm delivery.     

Adverse change in low-density lipoprotein subfractions profile with oestrogen-only hormone replacement therapy

In a prospective longitudinal study in 17 women, we investigated the effects of surgical menopause and subsequent oestrogen-only hormone replacement therapy (HRT) on plasma concentrations of total cholesterol, HDL cholesterol, LDL cholesterol, triglyceride and LDL subfractions profile. Plasma LDL is a heterogeneous population of particles of varying size, density and chemical composition. The predominance of small LDL particles is a newly-recognized risk factor for coronary artery disease. The LDL score is used to describe LDL subfractions profile and the greater the score, the higher the proportion of small LDL particles. Six weeks after hysterectomy and bilateral oopherectomy, total cholesterol and triglyceride concentrations were significantly increased (p < 0.01) as well as the LDL score (p < 0.05). After 6 weeks of oestrogen-only HRT, total cholesterol concentration was significantly lower and HDL cholesterol concentration significantly higher than before the treatment (p < 0.05). At the same time, mean LDL score significantly increased and in none of the women did LDL subfractions profile change favourably.