PET imaging of the dopamine transporter with 18F-FECNT: a polar radiometabolite confounds brain radioligand measurements.

18F-2beta-Carbomethoxy-3beta-(4-chlorophenyl)-8-(2-fluoroethyl)nortropane (18F-FECNT), a PET radioligand for the dopamine transporter (DAT), generates a radiometabolite that enters the rat brain. The aims of this study were to characterize this radiometabolite and to determine whether a similar phenomenon occurs in human and nonhuman primate brains by examining the stability of the apparent distribution volume in DAT-rich (striatum) and DAT-poor (cerebellum) regions of the brain. METHODS: Two rats were infused with 18F-FECNT and sacrificed at 60 min. Extracts of brain and plasma were analyzed by high-performance liquid chromatography (HPLC) and liquid chromatography-mass spectrometric (LC-MS) techniques. Two human participants and 3 rhesus monkeys were injected with 18F-FECNT and scanned kinetically, with serial arterial blood analysis. RESULTS: At 60 min after the injection of rats, 18F-FECNT accumulated to levels about 7 times higher in the striatum than in the cortex and cerebellum. The radiometabolite was distributed at equal concentrations in all brain regions. The LC-MS techniques identified N-dealkylated FECNT as a major metabolite in the rat brain, and reverse-phase HPLC detected an equivalent amount of radiometabolite eluting with the void volume. The radiometabolite likely was 18F-fluoroacetaldehyde, the product expected from the N-dealkylation of 18F-FECNT, or its oxidation product, 18F-fluoroacetic acid. The distribution volume in the cerebellum increased up to 1.7-fold in humans between 60 and 300 min after injection and 2.0 +/- 0.1-fold (mean +/- SD; n = 3) in nonhuman primates between 60 and 240 min after injection. CONCLUSION: An 18F-fluoroalkyl metabolite of 18F-FECNT originating in the periphery confounded the measurements of DAT in the rat brain with a reference tissue model. Its uniform distribution across brain regions suggests that it has negligible affinity for DAT (i.e., it is an inactive radiometabolite). Consistent with the rodent data, the apparent distribution volume in the cerebellum of both humans and nonhuman primates showed a continual increase at late times after injection, a result that may be attributed to entry of the radiometabolite into the brain. Thus, reference tissue modeling of 18F-FECNT will be prone to more errors than analysis with a measured arterial input function.     

Volume et profil de consommation d’alcool des élèves et des camarades scolaires comme prédicteurs de l’agression et de la victimisation: une analyse multiniveaux auprès d’adolescents suisses

Volume and profile of alcohol consumption among students and classmates as predictors of aggression and victimization: a multilevel analysis among Swiss adolescents

Objective:  

To test the effects of the volume of alcohol consumption and drinking patterns on alcohol-related aggression and victimization, both at the individual and class levels.     

Vacuum-assisted closure therapy in pyoderma gangrenosum

Vacuum-assisted closure (VAC), although a modern adjunct in wound management, has not been used previously in pyoderma gangrenosum (PG), probably to avoid the potential complications of ‘pathergy’. We would like to report our experience of VAC in three cases of PG with the relevant review of literature.     

Audio spectrum and sound pressure levels vary between pulse oximeters

PURPOSE: The variable-pitch pulse oximeter is an important intraoperative patient monitor. Our ability to hear its auditory signal depends on its acoustical properties and our hearing. This study quantitatively describes the audio spectrum and sound pressure levels of the monitoring tones produced by five variable-pitch pulse oximeters. METHODS: We compared the Datex-Ohmeda Capnomac Ultima, Hewlett-Packard M1166A, Datex-Engstrom AS/3, Ohmeda Biox 3700, and Datex-Ohmeda 3800 oximeters. Three machines of each of the five models were assessed for sound pressure levels (using a precision sound level meter) and audio spectrum (using a hanning windowed fast Fourier trans-form of three beats at saturations of 99%, 90%, and 85%). RESULTS: The widest range of sound pressure levels was produced by the Hewlett-Packard M1166A (46.5 +/- 1.74 dB to 76.9 +/- 2.77 dB). The loudest model was the Datex-Engstrom AS/3 (89.2 +/- 5.36 dB). Three oximeters, when set to the lower ranges of their volume settings, were indistinguishable from background operating room noise. Each model produced sounds with different audio spectra. Although each model produced a fundamental tone with multiple harmonic overtones, the number of harmonics varied with each model; from three harmonic tones on the Hewlett-Packard M1166A, to 12 on the Ohmeda Biox 3700. There were variations between models, and individual machines of the same model with respect to the fundamental tone associated with a given saturation. CONCLUSION: There is considerable variance in the sound pressure and audio spectrum of commercially-available pulse oximeters. Further studies are warranted in order to establish standards.     

Behandlung des Morbus Sudeck

Complex regional pain syndrome (CRPS) was formerly known as “Sudeck’s atrophy”. The disease belongs to the group of neuropathic pain syndromes and is differentiated into three types. Type I is characterized by a lack of nerve lesions, type II by the presence of nerve lesions, and type III by the presence of other entities such as fibromyalgia. The exact pathogenic factors leading to the disease are still unknown and are currently the subject of investigation in various studies. These studies suggest a contribution of the central nervous system to the development and maintenance of CRPS. However, the clinical symptoms are well documented and include pain, autonomic changes and impaired motor function of the affected extremity. Diagnosis is based clinically on signs and symptoms. However, in a few cases radiography and scintiscanning may be useful to finalize the diagnosis. The treatment options are centred on the symptoms of pain, autonomic changes and functional impairment. A multidisciplinary treatment strategy is recommended, with surgeons, anaesthesiologists, physiotherapists and psychotherapists working together. Surgical intervention in this disease is only required in rare cases of neurological and bone pain, and the indications for such intervention are narrow and should be strictly observed.     

Predictors of long-term survival in patients with gallbladder cancer

The aim of this study was to examine the predictors of long-term survival (>24 months) in patients with gall bladder cancer. A retrospective review of 117 cases of gall bladder cancer resected between 1989 and 2000. The resections included 80 simple cholecystectomies and 37 extended procedures. Patients with survival >24 months (n=44) were compared with those having survival <24 months (n=73) for 17 prognostic factors. Overall median survival was 16 months with a 5-year survival of 27%. T status (P=.000) and adjuvant chemoradiotherapy (P=.001) were independent predictors of long-term survival. Survival advantage was seen in T3N+ve disease (P=.007) with extended procedures. Complete (R0) resection was attained in 30 patients with a 5-year survival advantage of 30% as compared with incomplete (R1) resection (P=.0002). Adjuvant chemoradiotherapy improved survival in simple cholecystectomy group (P=.0008) but no advantage was seen after extended procedures. Stage III (P=.001) and node-positive disease (P=.0005) had significant benefit with adjuvant therapy. Poor differentiation and vascular invasion were associated with poor long-term survival. R0 resection was associated with prolonged survival. Extended procedures improved survival in patients with T3N+ve disease. Addition of chemoradiotherapy made significant improvement in long-term survival in stage III and node-positive lesions and in patients undergoing simple cholecystectomy. R0 resection predicted long-term survival in gall bladder cancer. T3 N+ve disease had better survival after extended procedures. Adjuvant chemoradiotherapy improved survival in stage III and node-positive disease. Poor differentiation and vascular invasion were adverse predictors of survival.     

Additive Effects of Sevoflurane and Propofol on γ-Aminobutyric Acid Receptor Function

Background: Previous studies have shown that propofol and sevoflurane enhance the function of [gamma]-aminobutyric acid type A (GABAA) receptors. However, it is not known whether these two drugs modulate the same molecular pathways. In addition, little is known about receptor function in the presence of both propofol and sevoflurane. The aim of this study was to better understand the interactions of propofol and sevoflurane with the GABAA receptor.

Methods: Wild-type [alpha]1, [beta]2, [gamma]2s GABAA receptor subunit complementary DNAs were transfected into human embryonic kidney cells grown on glass coverslips using a calcium phosphate transfection method. After transfection (36-72 h), cells were whole cell patch clamped and exposed to combinations of the following: 0.3-1,000 [mu]m [gamma]-aminobutyric acid (GABA), 0-10 [mu]m propofol, and 0-1,650 [mu]m sevoflurane. Chemicals were delivered to the cells using two 10-channel infusion pumps and a rapid solution exchanger.

Results: Both propofol and sevoflurane alone enhanced the amplitude of GABAA receptor responses to submaximal concentrations of GABA in a dose-dependent manner. The enhancement was underpinned by an increase in the apparent affinity of the receptor for GABA. Coapplication of both anesthetics further enhanced the apparent affinity of the receptor for GABA.     

Conversion from mycophenolate mofetil to enteric-coated mycophenolate sodium in liver transplant patients presenting gastrointestinal disorders: a pilot study.

Gastrointestinal (GI) disorders are one of the main adverse events in patients treated by mycophenolic acid (MPA). The aim of this prospective study was to evaluate the effect of conversion from mycophenolate mofetil (MMF) to enteric-coated mycophenolate sodium (EC-MPS) in liver transplant patients presenting GI side-effects Since January 2003, stable liver transplant patients receiving MMF and presenting GI disorders, without evidence of other origin than MMF were enrolled. Conversion was performed without a washout period at an equimolar daily dosage. Thirty-six patients were included after a median delay of 45 months after liver transplantation (LT) (16 women and 20 men, median age of 47 years). Diarrhoea was the main clinical symptom (n = 28, 77.7%). At the time of inclusion, patients were treated with MMF since 18 months (range 3-28) and GI disorders were known for 9 months (range 3-12). After a median follow-up of 12 months after conversion, GI disorders were resolved in 20 patients (55%), improved in 6 patients (17%) and not modified or worsened in 10 patients (28%). Our results strongly suggest that conversion from MMF to EC-MPS in liver transplant patients can improve gastrointestinal disorders in a majority of the patients, and therefore might be considered as the best therapeutic option.     

The Well-being Model: A New Drug Interaction Model for Positive and Negative Effects

Background: Drugs are routinely combined in anesthesia and pain management to obtain an enhancement of the desired effects. However, a parallel enhancement of the undesired effects might take place as well, resulting in a limited therapeutic usefulness. Therefore, when addressing the question of optimal drug combinations, side effects must be taken into account.

Methods: By extension of a previously published interaction model, the authors propose a method to study drug interactions considering also their side effects. A general outcome parameter identified as patient's well-being is defined by superposition of positive and negative effects. Well-being response surfaces are computed and analyzed for varying drugs pharmacodynamics and interaction types. In particular, the existence of multiple maxima and of optimal drug combinations is investigated for the combination of two drugs.

Results: Both drug pharmacodynamics and interaction type affect the well-being surface and the deriving optimal combinations. The effect of the interaction parameters can be explained in terms of synergy and antagonism and remains unchanged for varying pharmacodynamics. For all simulations performed for the combination of two drugs, the presence of more than one maximum was never observed.