Arsonoliposomes for the Potential Treatment of Medulloblastoma

Purpose  

To investigate the arsonoliposome effect on medulloblastoma cells (VC312Rs) related to uptake, endocytotic mechanism and cell viability.     

Highly specific quantification of ergotamine in urine, blood, and hair samples by liquid chromatography-tandem mass spectrometry

Ergotamine has been used for therapeutic purposes since the 1950s, usually to treat vascular headache. It is highly toxic and in large, repeated doses can produce all the symptoms of ergot poisoning. A selective and sensitive method, based on liquid chromatography-tandem mass spectrometry (LC-MS2), has been developed for quantifying ergotamine in biological fluids with use of a quick and easy sample preparation. Ergotamine and the internal standard, trideuterated lysergic acid diethylamide, were extracted from human urine, blood, and hair by means of liquid-liquid extraction at alkaline pH. Gradient elution on a cyanopropyl column was used for chromatographic separation. Positive ion electrospray ionization and tandem mass spectrometry determination by collision-induced dissociation were performed in an ion trap mass spectrometer. The method was validated and successfully applied to a case of iatrogenic ergotism resulting from the intake of ergotamine tartrate for treating headache. For the first time, ergotamine was identified and quantified in hair. The ergotamine concentrations measured were 320 pg/mL in blood, 100 pg/mL in urine, 24 pg/mg in proximal hair, and 15 pg/mg in distal hair.     

External recording and processing of fast electrical activity of the uterus in human parturition

The fast uterine electrical activity during parturition is analysed through two signals recorded on the abdominal wall. After differential amplification and filtration the fast activity is numerically processed to obtain quantified information for monitoring labour progress. Through parametric modellíng, the necessary data for the study of the EMG signal at each contraction is reduced to six. Moreover, an attempt was made to measure the velocity of electrical wave propagation across the uterus from the delay of the cross-correlation function maximum of the two signals.     

Pharmacogenetics of azathioprine in inflammatory bowel disease: A role for glutathione-S-transferase?

Azathioprine is a purine antimetabolite drug commonly used to treat inflammatory bowel disease(IBD).In vivo it is active after reaction with reduced glutathione(GSH)and conversion to mercaptopurine.Although this reaction may occur spontaneously,the presence of isoforms M and A of the enzyme glutathione-S-transferase(GST)may increase its speed.Indeed,in pediatric patients with IBD,deletion of GST-M1,which determines reduced enzymatic activity,was recently associated with reduced sensitivity to azathioprine and reduced production of azathioprine active metabolites.In addition to increase the activation of azathioprine to mercaptopurine,GSTs may contribute to azathioprine effects even by modulating GSH consumption,oxidative stress and apoptosis.Therefore,genetic polymorphisms in genes for GSTs may be useful to predict response to azathioprine even if more in vitro and clinical validation studies are needed.reserved.     

Stereotactic body radiation therapy for a new lung cancer arising after pneumonectomy: dosimetric evaluation and pulmonary toxicity

Objective:

To evaluate the tolerance of stereotactic body radiation therapy (SBRT) for the treatment of secondary lung tumours in patients who underwent previous pneumonectomy.

Methods:

12 patients were retrospectively analysed. The median maximum tumour diameter was 2.1 cm (1–4.5 cm). The median planning target volume was 20.7 cm³ (2.4–101.2 cm³). Five patients were treated with a single fraction of 26 Gy and seven patients with fractionated schemes (3 × 10 Gy, 4 × 10 Gy, 4 × 12 Gy). Lung toxicity, correlated with volume (V) of lung receiving >5, >10 and >20 Gy, local control and survival rate were assessed. Median follow-up was 28 months.

Results:

None of the patients experienced pulmonary toxicity > grade 2 at the median dosimetric lung parameters of V₅, V₁₀ and V₂₀ of 23.1% (range 10.7–56.7%), 7.3% (2.2–27.2%) and 2.7% (0.7–10.9%), respectively. No patients required oxygen or had deterioration of the performance status during follow-up if not as a result of clinical progression of disease. The local control probability at 2 years was 64.5%, and the overall survival at 2 years was 80%.

Conclusion:

SBRT appears to be a safe and effective modality for treating patients with a second lung tumour after pneumonectomy.

Advances in knowledge:

Our results and similar literature results show that when keeping V₅, V₁₀ V₂₀ <50%, <20% and <7%, respectively, the risk of significant lung toxicity is acceptable. Our experience also shows that biologically effective dose 10 >100 Gy, necessary for high local control rate, can be reached while complying with the dose constraints for most patients.     

N-hydroxyphenacetin, a new urinary metabolite of phenacetin in the rat

N-Hydroxyphenacetin has been found in the urine of rats dosed with phenacetin, extending previous reports that phenacetin is N-hydroxylated by liver microsomes in vitro. After an oral dose of phenacetin (500 mg/kg) urine was collected for 24 hr, conjugates hydrolyzed with extract of Helix pomatia, and the metabolites extracted with dichloromethane and treated with diazomethane. Methylation of N-hydroxyphenacetin produced a stable derivative, N-methoxyphenacetin, which was separated from most other metabolites by thin layer chromatography. Identification of N-methoxyphenacetin was by combined gas chromatography-mass spectrometry and comparison with the synthetic reference compound. Quantification by gas chromatography with flame-ionization detection showed that 0.023% of the dose phenacetin was recovered from urine as N-hydroxyphenacetin. It is probable that this value considerably underestimates the extent of phenacetin N-hydroxylation in vivo, inasmuch as N-hydroxyphenacetin is known to be rapidly degraded in biological systems.     

Pulmonary embolism: diagnostic algorithms.

In 90% of cases the clinical suspicion of pulmonary embolism (PE) is raised by clinical signs and symptoms, while in only 10% of cases PE is suspected on the basis of electrocardiographic, arterial blood gas analysis or radiological findings. The combination of clinical signs and symptoms and the results of first-level diagnostic tests (electrocardiography, gas analysis and chest X-ray) allows a fairly accurate classification of patients with "clinical suspicion of PE" into three categories of clinical (or pre-test) probability: low, intermediate and high. The clinical diagnosis of PE is very often inaccurate making the use of additional tests, including imaging techniques, mandatory. The choice and the combination (= diagnostic algorithms) of second- and third-level diagnostic tests (D-dimer, venous ultrasound, echocardiography, lung scintigraphy, helical computed tomography and pulmonary angiography) depend primarily on the clinical conditions of patients and their pre-test probability. We propose two diagnostic algorithms: 1) a diagnostic algorithm for patients with clinically suspected PE and critical clinical conditions (unstable patients), 2) a diagnostic algorithm for patients with clinically suspected PE and non-critical clinical conditions (hemodynamically stable patients).     

Association between depression and heart rate variability in patients after cardiac surgery: a pilot study

ObjectiveDepression is a risk factor for cardiovascular diseases. Reduced heart rate variability (HRV), which reflects altered autonomic nervous system activity, has been suggested as one of the mechanisms linking depression to cardiovascular diseases. However, the relationship between depression and HRV has not yet been investigated in patients undergone cardiac surgery. Therefore, the main aim of this study was to examine whether postoperative depression could be related to reduced HRV.MethodsEleven patients with depression and 22 patients without depression, who had undergone cardiac surgery, were enrolled postoperatively. In all patients, HRV was derived from a four-minute blood volume pulse recording at rest. Analyses of covariance and partial correlations, while controlling for anxiety, were used to examine the associations between postoperative depression and each HRV parameter.ResultsCompared to non-depressed patients, patients with depression showed significantly lower standard deviation of N-to-N intervals (SDNN) (p = .02), root mean square successive difference of N-to-N intervals (rMSSD) (p = .001), and high‐frequency power (p = .002). Partial correlation analyses showed that depression was inversely related to SDNN (r = ? .49, p = .005), rMSSD (r = ? .58, p = .001), and high‐frequency power (r = ? .41, p = .02), whereas it was unrelated to other HRV parameters (p's > .09).ConclusionsThe current findings extend the depression-reduced HRV relationship to the patients after cardiac surgery. Also, our study suggests that postoperative depression is more likely to be associated with reduced vagal modulation on the heart than with excessive sympathetic activity.