CHROMOSOME 3 MAY HARBOR MULTIPLE TUMOR SUPPRESSOR GENES ASSOCIATED WITH PRIMARY GLIOBLASTOMA MULTIFORME

Glioblastoma multiforme (GBM), the most malignant type of glioma, is the most common primary brainneoplasm. Although comprehensive therapeutic measures are applied, the prognosis of GBM remains dismal with a median post-treatment survival of less than one year.Modern molecular genetics has demonstrated thatabnormal alterations of tumor suppressor genes (TSGs) and oncogenes are the major mechanisms responsible for the initiation and progression of this malignant tumor.Identifying of related…     

Promising hypotensive effect of hawthorn extract: a randomized double-blind pilot study of mild, essential hypertension.

This pilot study was aimed at investigating the hypotensive potential of hawthorn extract and magnesium dietary supplements individually and in combination, compared with a placebo. Thirty-six mildly hypertensive subjects completed the study. At baseline, anthropometric and dietary assessment, as well as blood pressure measurements were taken at rest, after exercise and after a computer 'stress' test. Volunteers were then randomly assigned to a daily supplement for 10 weeks of either: (a) 600 mg Mg, (b) 500 mg hawthorn extract, (c) a combination of (a) and (b), (d) placebo. Measurements were repeated at 5 and 10 weeks of intervention. There was a decline in both systolic and diastolic blood pressure in all treatment groups, including placebo, but ANOVA provided no evidence of difference between treatments. However, factorial contrast analysis in ANOVA showed a promising reduction (p = 0.081) in the resting diastolic blood pressure at week 10 in the 19 subjects who were assigned to the hawthorn extract, compared with the other groups. Furthermore, a trend towards a reduction in anxiety (p = 0.094) was also observed in those taking hawthorn compared with the other groups. These findings warrant further study, particularly in view of the low dose of hawthorn extract used.     

The laryngeal mask airway in the difficult paediatric airway: an assessment of positioning and use in fibreoptic intubation

The laryngeal mask airway (LMA) was used in 34 children who presented with difficult airways and difficulty in intubation. All 34 children were a grade 3 or grade 4 Cormack and Leehane view at conventional laryngoscopy. The laryngeal mask airway was used as part of the anaesthetic technique. It was either used as the method of airway maintenance during a short procedure or as an aid to fibreoptic intubation. The results of its use in this group of patients showed that overall a good airway was obtained in 73% of patients and an adequate airway in 27%, and in no patient was a poor airway obtained. The fibreoptic positioning of the LMA, taken from the distal aperture of the laryngeal mask airway showed that, overall, in 29.5% of patients a full view of the glottis (grade 1) was obtained, in 29.5% of patients a partial view of the glottis (grade 2) was obtained and in 41% a view of the epiglottis only (grade 3) was obtained. In no patient was a view excluding the epiglottis obtained. In children with a mucopolysaccharide disorder, the number of children who had a grade 3 view increased to 54%. Children with a disorder other than mucopolysaccharidosis had a grade 3 view in only 17% of cases. Children with mucopolysaccharidoses had a grade 1 view in only 14% of cases compared with 58% in the group with other disorders. Of the 34 patients, 21 patients were intubated on 31 separate occasions. There were no failures. The complications of the fibreoptic intubation technique described are outlined.     

Sertraline treatment of generalized social phobia: a 20-week, double-blind, placebo-controlled study

OBJECTIVE: The authors evaluated the efficacy, safety, and tolerability of sertraline, a selective serotonin reuptake inhibitor, in the treatment of generalized social phobia. METHOD: Adult outpatients with generalized social phobia (N=204) from 10 Canadian centers were randomly assigned to receive sertraline or placebo in a 2:1 ratio for a 20-week double-blind study following a 1-week, single-blind, placebo run-in. The initial dose of sertraline was 50 mg/day with increases of 50 mg/day every 3 weeks permitted after the fourth week of treatment (dosing was flexible up to a maximum of 200 mg/day). Primary efficacy assessments were the percentage of patients rated much or very much improved on the Clinical Global Impression (CGI) improvement item and the mean changes from baseline to study endpoint in total score on the social phobia subscale of the Marks Fear Questionnaire and total score on the Brief Social Phobia Scale. RESULTS: In intent-to-treat endpoint analyses of 203 of the patients, significantly more of the 134 patients given sertraline (N=71 [53%]) than of the 69 patients receiving placebo (N=20 [29%]) were considered responders according to their CGI improvement scores at the end of treatment. The mean reductions in the social phobia subscale of the Marks Fear Questionnaire and in the total score on the Brief Social Phobia Scale were 32.6% and 34.3% in the sertraline group and 10.8% and 18.6% in the placebo group, respectively. Analysis of covariance showed superiority of sertraline over placebo on all primary and secondary efficacy measures. Sertraline was well tolerated: 103 (76%) of the 135 sertraline-treated patients and 54 (78%) of the 69 placebo-treated patients completed the study. CONCLUSIONS: Sertraline is an effective treatment for patients with generalized social phobia.     

Magnetic source imaging of late evoked field responses to vowels: toward an assessment of hemispheric dominance for language

OBJECT: The goal of this study was to determine whether the late neuromagnetic field elicited by simple speech sounds, which is detected by magnetoencephalography, may be used to estimate hemispheric dominance for language and to guide or constrain the intraoperative search for essential language sites. If sufficiently robust, a noninvasive method for assessing hemispheric dominance for language could reduce the necessity for amobarbital testing and the extent of intraoperative cortical stimulation-based mapping, both of which carry the risk of morbidity. METHODS: Fifteen patients undergoing surgery for tumors during which intraoperative language mapping would be performed and two additional patients in whom intracarotid amobarbital testing confirmed right-hemisphere language dominance participated. Following a primary auditory response sources of late neuromagnetic fields elicited by vowel stimuli were modeled and coregistered using magnetic resonance images to form magnetic source (MS) images. A laterality index (LI) was calculated by summing the number of equivalent current dipolar sources in the late fields detected from each hemisphere. In 14 right-handed patients, 10 displayed left asymmetric LIs (0.37 +/- 0.16. mean +/- standard error of the mean in 14 patients). For both right-hemisphere dominant patients in whom an LI was obtainable, the LI was rightward. Stimulation-mapped essential language sites were found in 7 of 15 patients. For six of these seven patients, the MS image-derived LI was leftward. CONCLUSIONS: Asymmetry in single equivalent dipole modeling of the late neuromagnetic field evoked by simple speech sounds correlates with hemispheric language dominance, although not to the degree necessary for individual clinical predictions. With further development, MS imaging of simple language tasks may be used preoperatively to predict language dominance and even to identify or constrain the intraoperative search for likely sites of essential language cortex.     

Urethral calculi managed with transurethral Holmium laser ablation

In situ Holmium laser lithotripsy is a safe, effective procedure for the treatment of impacted urethral stones. This procedure can be performed transurethrally as an outpatient with minimal tissue trauma and render patients stone free. The authors utilized this procedure in 2 patients whose anatomy did not allow the calculi to be manipulated into the urinary bladder in a retrograde manner. Because of its successful use elsewhere in the urinary tract, we believe that Holmium laser lithotripsy may be the treatment of choice for impacted urethral stones.     

The novel glycolipid RC-552 attenuates myocardial stunning and reduces infarct size in dogs

The novel glycolipid RC-552 shares common structural features with the natural products lipid A and the previously described cardioprotectant monophosphoryl lipid A. RC-552 administered to dogs as a bolus intravenous dose (35-70 microg/kg) either 24 h or 10 min prior to 60 min of regional myocardial ischemia and 3 h of reperfusion significantly (P<0.05 v control) reduced infarct size (IS) as assessed by triphenyltetrazolium staining from 27.0+/-2.3% of the area-at-risk (AAR) to 13.3+/-2.2% and 15.0+/-3.0%, respectively. Administration of the non-specific inducible nitric oxide synthase (iNOS) inhibitor aminoguanidine (30 mg/kg, subcutaneously) 1 h prior to ischemia blocked the ability of RC-552 (35 microg/kg, 24 h pretreatment) to reduce infarct size. Intravenous pretreatment with RC-552 (35 microg/kg) either 24 h or 10 min prior to five 5 min repetitive cycles of ischemia and reperfusion significantly improved regional myocardial segment shortening (percentage of control) at all time points during 2 h of reperfusion in dogs. These effects of RC-552 in either cardiac injury model occurred independent of differences in AAR, transmural blood flow during ischemia or hemodynamics throughout the experiment. In contrast with monophosphoryl lipid A (MLA), which has also been reported to be cardioprotective at similar doses in dogs, RC-552 was approximately 100 times less prone to cause fever in the USP rabbit pyrogen test. Likewise, RC-552 did not induce secretion of the proinflammatory cytokines TNF, IL-6 or IL-8 from THP-1 cells or alter the expression of adhesion molecules on human neutrophils at concentrations up to 10 microg/ml. MLA was active in these systems at concentrations in the range 0.1-1.0 microg/ml. In conclusion, RC-552 reduces myocardial infarct size and stunning in dogs in the absence of residual immunomodulatory activity.