Increased glutamate/glutamine compounds in the brains of patients with fibromyalgia: A magnetic resonance spectroscopy study

Objective

Fibromyalgia (FM) has been defined as a systemic disorder that is clinically characterized by pain, cognitive deficit, and the presence of associated psychopathology, all of which are suggestive of a primary brain dysfunction. This study was undertaken to identify the nature of this cerebral dysfunction by assessing the brain metabolite patterns in patients with FM through magnetic resonance spectroscopy (MRS) techniques.

Methods

A cohort of 28 female patients with FM and a control group of 24 healthy women of the same age were studied. MRS techniques were used to study brain metabolites in the amygdala, thalami, and prefrontal cortex of these women.

Results

In comparison with healthy controls, patients with FM showed higher levels of glutamate/glutamine (Glx) compounds (mean ± SD 11.9 ± 1.6 arbitrary units [AU] versus 13.4 ± 1.7 AU in controls and patients, respectively; t = 2.517, 35 df, corrected P = 0.03) and a higher Glx:creatine ratio (mean ± SD 2.1 ± 0.4 versus 2.4 ± 1.4, respectively; t = 2.373, 35 df, corrected P = 0.04) in the right amygdala. In FM patients with increased levels of pain intensity, greater fatigue, and more symptoms of depression, inositol levels in the right amygdala and right thalamus were significantly higher.

Conclusion

The distinctive metabolic features found in the right amygdala of patients with FM suggest the possible existence of a neural dysfunction in emotional processing. The results appear to extend previous findings regarding the dysfunction in pain processing observed in patients with FM.

     

Phase I/II docetaxel plus concurrent hyperfractionated radiotherapy in locally advanced unresectable head and neck cancer (TAX.ES1.102 study)

Introduction

Concurrent chemotherapy and radiotherapy is recommended for the treatment of locally advanced unresectable head and neck (H&N) cancer.

Objective

The primary purpose of the Phase I part of the study was to determine the maximum tolerated dose (MTD), dose-limiting toxicity (DLT) and recommended dose (RD) of docetaxel with hyperfractionation radiotherapy. The primary objective of the Phase II part was to determine the response rate to the RD of treatment and, secondarily, to assess the toxicity of the schedule, time to progression, duration of response and overall survival (OS).

Materials and methods

Patients (n=9 in Phase I; n=19 in Phase II) had unresectable H&N cancer. The starting docetaxel dose was 20 mg/m² plus hyperfractionated radiotherapy. Ramping of docetaxel was 5 mg/m² if MTD was not reached.

Results

MTD of docetaxel was 20 mg/m². Limiting toxicities were grade 4 pneumonia and grade 4 mucositis. The RD was 15 mg/m2. Phase II initial response was 76% (CR=18%; PR=9%); updated response was 89% (CR=59%; PR=29%). The median progression-free survival was 7.8 months (95%CI: 0?C22.3) and the median OS was 15.1 months (95%CI: 0?C35.9). Grade 3?C4 toxicities included mucositis (91%), pneumonia (27%) and fatigue (27%). There were 5 toxic deaths (2 from intestinal perforation, 3 from pneumonia).

Conclusions

Weekly docetaxel+hyperfractionation radiotherapy is active but with high toxicity rates and, hence, this treatment regimen would be difficult to justify.     

Disposition of gamma-hydroxybutyric acid in conventional and nonconventional biologic fluids after single drug administration: issues in methodology and drug monitoring

Little controlled drug administration data are available to aid in the interpretation of gamma-hydroxybutyric acid (GHB) distribution in conventional and nonconventional fluids and the potential correlation between the pharmacokinetics of GHB and drug effects. Single oral sodium GHB doses of 50 mg/kg were administered to five volunteers. Plasma, oral fluid, urine, and sweat were analyzed for GHB by gas chromatography-mass spectrometry. GHB stability in plasma was studied at different storage temperatures. Subjective effects were measured using a set of 13 different visual analog scales. Mean peak GHB plasma concentrations at 30 minutes were 83.1 microg/mL. After the absorption phase, concentrations declined to mean values of 0.9 microg/mL at 6 hours. GHB was found in oral fluid at peak value concentrations equivalent to one third to one fourth of those found in plasma. The oral fluid-to-plasma ratio varied two fold in the 1- to 6-hour time range but always was lower than unit. The mean half-life (t1/2) of GHB was approximately 0.7 hour in plasma and approximately 1.2 hours in oral fluid. GHB urinary excretion is less than 2% of the dose administered. GHB was also detected in sweat at low concentrations. GHB showed a mixed sedative-stimulant pattern with subjective effects peaking between 1 and 1.5 hours after drug administration and lasting for 2 hours. Oral fluid and sweat appeared not to be suitable biologic matrices for monitoring GHB consumption. GHB-mediated subjective effects are related to GHB plasma concentrations.     

Different hip and knee priority score systems: are they good for the same thing?

Objective The aim of the present study was to compare two priority tools used for joint replacement for patients on waiting lists, which use two different methods. Methods Two prioritization tools developed and validated by different methodologies were used on the same cohort of patients. The first, an IRYSS hip and knee priority score (IHKPS) developed by RAND method, was applied while patients were on the waiting list. The other, a Catalonia hip–knee priority score (CHKPS) developed by conjoint analysis, was adapted and applied retrospectively. In addition, all patients fulfilled pre‐intervention the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Correlation between them was studied by Pearson correlation coefficient (r). Agreement was analysed by means of intra‐class correlation coefficient (ICC), Kendall coefficient and Cohern kappa. The relationship between IHKPS, CHKPS and baseline WOMAC scores by r coefficient was studied. Results The sample consisted of 774 consecutive patients. Pearson correlation coefficient between IHKPS and CHKPS was 0.79. The agreement study showed that ICC was 0.74, Kendall coefficient 0.86 and kappa 0.66. Finally, correlation between CHKPS and baseline WOMAC ranged from 0.43 to 0.64. The results according to the relationship between IHKPS and WOMAC ranged from 0.50 to 0.74. Conclusions Results support the hypothesis that if the final objective of the prioritization tools is to organize and sort patients on the waiting list, although they use different methodologies, the results are similar.