We describe a novel constitutive model of lung parenchyma, which can be used for continuum mechanics based predictive simulations. To develop this model, we experimentally determined the nonlinear material behavior of rat lung parenchyma. This was achieved via uni-axial tension tests on living precision-cut rat lung slices. The resulting force-displacement curves were then used as inputs for an inverse analysis. The Levenberg-Marquardt algorithm was utilized to optimize the material parameters of combinations and recombinations of established strain-energy density functions (SEFs). Comparing the best-fits of the tested SEFs we found Wpar = 4.1 kPa(I1-3)2 + 20.7 kPa(I1 - 3)3 + 4.1 kPa(-2 ln J + J2 - 1) to be the optimal constitutive model. This SEF consists of three summands: the first can be interpreted as the contribution of the elastin fibers and the ground substance, the second as the contribution of the collagen fibers while the third controls the volumetric change. The presented approach will help to model the behavior of the pulmonary parenchyma and to quantify the strains and stresses during ventilation.

The external static electric field (SEF) of man-made origin brings to the substantially increased SEF background in a human environment the biological activity of which is a moot question. The paper reports on rats blood plasma/serum proteome modifications by means of 1D polyacrilamide gel electrophoresis and clotting process alterations after the short- and long-term SEF exposures of 200 kV/m. The results indicate decrease of fast α1 and α2 globular proteins in plasma coinciding with clotting acceleration after the short-term SEF, and attenuation of clotting-dependent proteome modifications reflected with incomplete coagulation after the long-term SEF exposure. Increased lysozyme activity in serum unlike plasma was observed after both SEF exposures. Applied model of the high-voltage SEF environment indicates dependence of biological systems functioning on the external SEF.

The purpose of this study is to investigate the primary somatosensory function in patients with unilateral polymicrogyria. Somatosensory evoked fields (SEFs) due to median and posterior tibial nerve stimulation were compared in the normal and dysplastic cortices of five patients with unilateral polymicrogyria. SEFs were observed in all five normal hemispheres and three dysplastic hemispheres. Latencies of N20m and P38m, the first cortical components of and SEFs for median nerve and tibial nerve stimulation, were all within the normal range in both normal and dysplastic hemispheres. The amplitudes of the N20m and P38m in the dysplastic hemispheres were smaller in one patient and larger in two patients compared to the normal hemispheres. Equivalent current dipoles of N20m and P38m were localized on the anatomical central sulcus of the normal hemispheres and over the central area of the dysplastic hemispheres. P38m dipoles were localized medial and upward to the N20m dipole in both normal and dysplastic hemispheres. N20m dipole orientation was normal in all normal hemispheres and in one dysplastic hemisphere, but abnormally inferior in two dysplastic hemispheres. P38m dipole had normal medial orientation in all hemispheres except one dysplastic hemisphere. Abnormality of the primary somatosensory function in the dysplastic cortex of patients with unilateral polymicrogyria was clearly demonstrated by magnetoencephalography with high resolution in time and space. The normal somatotopic arrangement was preserved.

Sclerosing epithelioid fibrosarcoma (SEF) is a rare and poorly defined variant of fibrosarcoma, but generally insensitive to chemotherapy and progresses with poor prognosis. We report the marvelous effect of irinotecan hydrochloride (CPT-11) chemotherapy in rescuing a patient with atypical SEF from emergent condition, who underwent recurrences after several treatment methods. Small dose of CPT-11 was administered to the patient, with which, the size of superficial mass (cervical lymph node) gradually decreased observed by the naked eyes in 5 days. X-ray and CT image proved a marked reduction in the size of the tumor. CPT-11 is valuable for the treatment of this aggressive sarcoma. In condition of emergency caused by sarcoma oppression, administering a tolerable small dose of topoisomerase I-inhibiting drug could be a beneficial choice.

BACKGROUND

Monitoring assisted reproductive technology (ART) is essential to evaluate the performance of fertility treatment and its impact on birth rates. In Europe, there are two kinds of ART registers: voluntary and mandatory. The validity of register data is very important with respect to the quality of register-based observational studies. The aim of this paper is to determine the degree of agreement between voluntary and mandatory ART registers.

METHODS

The two sources for the data compared in this study (referring to 2005 and 2006) were FIVCAT.NET (an official compulsory Assisted Reproduction Registry within the Health Ministry of the Regional Government of Catalonia, to which all authorized clinics, both public and private, performing assisted reproduction in the region are obliged to report) and the register of the Spanish Fertility Society (SEF), to which data are provided on a voluntary basis. The SEF register data were divided into two groups: (i) data from clinics in Catalonia (SEF-CAT); (ii) data from the rest of Spain, excluding Catalonia (SEF-wCAT). The techniques compared were IVF cycle using patients' own eggs (IVF cycle) versus donor egg cycles.

RESULTS

For IVF cycles, the voluntary ART register reflected 77.2% of those on the official one, but the corresponding figure was only 34.4% with respect to donated eggs. The variables analysed in the IVF cycle (insemination technique used, patients' age, number of embryos transferred, pregnancy rates, multiple pregnancies and deliveries) were similar in the three groups studied. However, we observed significant differences in donor egg cycles with regard to the insemination technique used, pregnancy rates and multiple pregnancies between the voluntary and the official register.

CONCLUSIONS

Data from the voluntary ART register for IVF cycles are valid, but those for donor egg cycles are not. Further study is necessary to determine the reasons for this difference.

OBJECTIVE

To estimate dose-response relationship using dynamic quantitative (99m)Tc-pertechnate scintigraphy in head-neck cancer patients treated with parotid-sparing conformal radiotherapy.

METHODS

Dynamic quantitative pertechnate salivary scintigraphy was performed pre-treatment and subsequently periodically after definitive radiotherapy. Reduction in salivary function following radiotherapy was quantified by salivary excretion fraction (SEF) ratios. Dose-response curves were modeled using standardized methodology to calculate tolerance dose 50 (TD50) for parotid glands.

RESULTS

Salivary gland function was significantly affected by radiotherapy with maximal decrease in SEF ratios at 3-months, with moderate functional recovery over time. There was significant inverse correlation between SEF ratios and mean parotid doses at 3-months (r = -0.589, p<0.001); 12-months (r = -0.554, p<0.001); 24-months (r = -0.371, p = 0.002); and 36-months (r=-0.350, p=0.005) respectively. Using a post-treatment SEF ratio <45% as the scintigraphic criteria to define severe salivary toxicity, the estimated TD50 value with its 95% confidence interval (95% CI) for the parotid gland was 35.1Gy (23.6-42.6Gy), 41.3Gy (34.6-48.8Gy), 55.9Gy (47.4-70.0Gy) and 64.3Gy (55.8-70.0Gy) at 3, 12, 24, and 36-months respectively.

CONCLUSIONS

There is consistent decline in parotid function even after conformal radiotherapy with moderate recovery over time. Dynamic quantitative pertechnate scintigraphy is a simple, reproducible, and minimally invasive test of major salivary gland function.

Quantitative measurement is required in clinical situation for sensory disturbance of the tongue due to lingual nerve injury. To assess disabled sensory function of the tongue, somatosensory evoked magnetic fields (SEFs) were measured following electric tongue stimulation in 13 patients with sensory disturbance by unilateral lingual nerve injury and in 10 age-matched healthy volunteers. Affected- and healthy-sides of the tongue were stimulated separately with the same intensity. Although the healthy-side stimulation induced clear responses over the contralateral hemisphere of all participants, the affected-side stimulation evoked hardly traceable responses in 6 patients and no activity in the remaining 7 patients. We evaluated the cortical activity via activated root-mean-square (aRMS), which is the time-averaged activity between 10 and 150 ms from the 18-channel RMS over the contralateral hemisphere. The laterality index of aRMS, expressed as [(left-right)/(left+right)], was out of the pre-defined normal range (-0.287 to 0.337) in 12 patients, and within the range in all healthy volunteers. The test sensitivity and specificity of the procedure were 92.3% and 100%, respectively. Tongue SEFs are reproducible and objective method to evaluate sensory disturbance of the tongue.

OBJECTIVE

Identification of a detailed topography of the receptive area for each of the thoracic dermatomes in humans using somatosensory evoked magnetic fields (SEF).

METHODS

We analyzed the location of the equivalent current dipole (ECD) of SEF following electrical stimulation of the skin at Th4, Th6, Th8, Th10 and Th12 dermatomes in 14 normal subjects.

RESULTS

Three deflections, M18, M25 and M40, were obtained within 60 ms of stimulation of Th6, Th8 and Th10 dermatomes. No consistent deflection could be identified following Th4 and Th12 dermatomal stimulation, probably due to a poor signal-to-noise ratio and difficulty in fixing the stimulation electrodes. M18 was absent or small in amplitude. The latency of M25 ranged from short to long in the order Th6, Th8 and Th10 (P<0.05). ECDs of all components for each site stimulation were located in the truncal area of the primary somatosensory cortex. Although the locations of the ECDs tend to be arranged from lateral to medial in the sequence Th6, Th8 and Th10, the difference was not significant.

CONCLUSIONS

The representation area of the trunk is small, and the receptive areas for the stimulation of Th6, Th8 and Th10 dermatomes are considered to be very close or to overlap.

This study compares brain activation patterns evoked by smooth pursuit and by fixation suppression of the optokinetic reflex (OKR) using similar retinal stimulation. Functional magnetic resonance imaging (fMRI) was performed during smooth pursuit stimulation in which a moving target was presented on a stationary pattern of stripes, and during fixation suppression of OKR in which a stationary target was presented on a moving pattern of stripes. All subjects could effectively ignore the background pattern and were able to keep the target continuously on the fovea with few saccades, in both experiments. Smooth pursuit evoked activation in the frontal eye fields (FEF), the supplementary eye fields (SEF), the parietal eye fields (PEF), the motion-sensitive area (MT/V5), and in lobules and vermis VI of the cerebellum (oculomotor areas). Fixation suppression of OKR induced activation in the FEF, PEF, and MT/V5. The direct comparison analysis revealed more activation in the right lobule VI of the cerebellum and in the right lingual and calcarine gyri during smooth pursuit than during fixation suppression of OKR. Using similar retinal stimulation, our results show that smooth pursuit and fixation suppression of the OKR appear to activate largely overlapping pathways. The increased activity in the oculomotor areas of the cerebellum during smooth pursuit is probably due to the presence of an active eye movement component.

The effects of noxious surgical stimulation on the electroencephalogram (EEG) in 15 horses anesthetized with isoflurane were evaluated during orthopedic (group 1) and soft tissue (group 2) procedures. The quantitative EEG variables theta/delta ratio (T/D), alpha/delta ratio (A/D), beta/delta ratio (B/D), median power frequency (MED), and 80% spectral edge frequency (SEF 80) recorded during Surgeries at 1.7% end-tidal concentration of isoflurane (ET(iso)) were compared with values from five nonstimulated control horses anesthetized at 1,7% ET(iso). The EEG variables T/D, A/D, MED, and SEF 80 from surgically stimulated horses were significantly higher compared with controls. These differences in measured EEG variables were accompanied by a significantly lower relative power in the delta frequency band and a concomitant significantly higher alpha activity. Because the A/D ratio, MED, and SEF 80 in surgically stimulated horses were significantly higher than in nonstimulated control horses these measured EEG variables may provide a valuable tool for identification of nociceptive transmission in isoflurane anesthetized horses.

Smooth pursuit eye movements function to keep moving targets foveated. Behavioral studies have shown that pursuit is particularly effective for predictable target motion. There is evidence that both the frontal eye field (FEF) and supplementary eye field (SEF) (also known as the dorsomedial frontal cortex) contribute to pursuit control. The goal of the current experiment was to determine whether these 2 areas made different contributions to the initiation of pursuit in response to predictable compared with unpredictable target motion. Transcranial magnetic stimulation (TMS) was used in 5 healthy human participants to temporarily disrupt each area around the time of target motion onset. TMS over the FEF delayed contraversive pursuit markedly more than ipsiversive pursuit and this direction-dependent difference was more deeply modulated during pursuit of unpredictable than predictable target motion. By contrast, TMS over the SEF resulted in a much more muted modulation of pursuit latency that was similar across both predictable and unpredictable conditions. Taken together, we conclude that the human FEF, but not the SEF, makes a significant contribution to the processing required during the preparation of contraversive pursuit responses to unpredictable target motion and this contribution is less vital during pursuit to predictable target motion.

The aim of this study is to localize the primary sensory cortex of urogenital organs in the human brain. Using a newly developed MRI-linked magnetoencephalography system, we measured somatosensory evoked magnetic fields (SEFs) for unilateral stimuli on the dorsal penile nerve (DPN), posterior tibial nerve (PTN) and median nerve (MN). In five healthy male subjects, SEFs were clearly observed. Peak latency of the first cortical components were 63.8 +/- 9.2 ms for DPN, 39.8 +/- 3.0 ms for PTN and 20.7 +/- 0.7 ms for MN stimuli. Peak amplitude of the first cortical components were 63.1 +/- 10.8 fT for DPN, 160.2 +/- 50.1 fT for PTN and 335.2 +/- 70.3 fT for MN stimuli. Isofield map for the peak latencies indicated a single dipolar pattern for DPN as well as for PTN and MN stimuli. Using a single current dipole model, all SEF sources were localized on the contralateral central sulcus to the stimuli, indicating the primary sensory cortex. The DPN sources were localized on the interhemispheric surfaces, corresponding to previous speculations by direct cerebral stimulation. This non-invasive SEF technique promises further brain functional mapping for the urogenital organs.

BACKGROUND

The objective of anaesthesia is to provide hypnosis, analgesia and adequate conditions during surgery. It is difficult to establish the appropriate dose of general anaesthetic drugs in the morbidly obese patient. Moreover, there are conflicting data concerning adequate anaesthesia levels and the severity of postoperative pain. The aim of this study was to investigate the relationship between the spectral edge frequency (SEF) during general anaesthesia and the severity of immediate postoperative pain following gastric banding surgery in morbidly obese patients.

METHODS

Seventy-one ASA 2 morbidly obese patients (BMI>> 35%) undergoing elective laparoscopic gastric banding procedure were recruited for this study. Anaesthesia consisted of midazolam, fentanyl and thiopental for induction, vecuronium for muscle relaxation, N2O and isoflurane with additional fentanyl administrations, according to the clinical judgement of the anaesthesiologist, for maintenance. Continuous SEF monitoring was added to the standard monitors (SpO2, ETCO2, ECG, NIBP, O2 and isoflurane concentration), but the EEG monitor screen was hidden from the anaesthesiologist's sight. SEF postoperative analysis divided the patients into two groups: group 1, SEF-recommended target range of 8-12 Hz, more than 80% of the surgical time; and group 2, SEF-recommended target range of 8-12 Hz, less than 80% of the surgery duration. Pain intensity was assessed in the post anaesthesia care unit using a standard visual analogue scale (VAS) of 10 cm, when patients were awake enough to correct a deliberately given wrong own telephone or ID number. Intravenous morphine was administered for postoperative analgesia in 2-mg increments, every 3-4 min, until the patient felt comfortable. A recovery room nurse unaware of the SEF range recorded during surgery registered pain severity and morphine requirements.

RESULTS

The end-tidal isoflurane concentration was significantly higher in group 1 than in group 2 (0.83 vs. 0.7 P = 0.016). The intensity of pain at admission into the recovery room and at discharge was significantly lower in group 1 than in group 2 (VAS 6.1 vs. 6.9-P = 0.0049, and 3.9 vs. 4.2-P = 0.00478, respectively).

CONCLUSIONS

Keeping the SEF range between 8 and 12 Hz during anaesthesia for laparoscopic gastric banding for morbid obesity, both the immediate post operative pain intensity and morphine requirement, are significantly reduced.

OBJECTIVE

Cancer anorexia-cachexia syndrome (CACS) is common in advanced cancer patients and associated with weight loss, fatigue, impaired quality of life (QoL), and poor prognosis. The goal of this project was to identify the most responsive items from two QoL measures in the ROMANA 2 (NCT01387282) phase III global study evaluating anamorelin HCl in the treatment of non-small cell lung cancer (NSCLC) cachexia: the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) and the Functional Assessment of Anorexia/Cachexia Therapy (FAACT).

METHODS

In the ROMANA 2 trial, 477 patients with unresectable stage III or IV NSCLC and cachexia were to be enrolled and randomized (2:1) to receive anamorelin HCl or placebo once daily for 12 weeks. All 203 patients who reached the week 12 visit at the time of data analysis were included. Co-primary endpoints were change from baseline in lean body mass and handgrip strength. QoL was a secondary outcome with FACIT-F and FAACT questionnaires administered at baseline and at weeks 3, 6, 9, and 12.

RESULTS

Two 4-item scales (fatigue/activity and appetite/eating) from the FACIT-F and FAACT questionnaires, respectively, demonstrated good internal consistency reliability, validity, and responsiveness (also referred to as the Simplified Evaluation of Fatigue (SEF) and Simplified Evaluation of Appetite (SEA), respectively). The estimated important difference for each scale was 1-2 points.

CONCLUSIONS

These brief scales provide the psychometric properties necessary to promote future research in NSCLC patients with CACS. Additional work should examine the clinical utility of these scales and their impact on treatment decision-making.

Despite association with adverse clinical outcome, human immunodeficiency virus (HIV)-associated malnutrition has been relatively refractory to conventional nutrition management. Consequently, a prospective randomized trial was conducted to evaluate a new peptide-based enteral formula (NEF) in contrast to a standard enteral formula (SEF) in patients with HIV infection. Eighty early-stage largely asymptomatic patients were randomized into a dietary regimen supplemented with either a ready-to-feed NEF (18.7% protein, 65.5% carbohydrate, 15.8% fat; 1.28 kcal/ml) or SEF (14% protein, 55% carbohydrate, 31% fat; 1.06 kcal/ml). Patients received 2-3 8-oz cans of the NEF or SEF supplement per day for 6 mo. Parameters evaluated at 0 (baseline), 3, and 6 mo included adherence, weight change, anthropometric measurements, serum biochemical indices, gastrointestinal symptoms, physical performance, and intercurrent health events (including hospitalizations). For the 56 evaluable patients, those supplemented with NEF maintained their body weight significantly (p = 0.04) better, had significantly (p = 0.03) more stable triceps skin-fold measurements, and had significantly (p = 0.04) lower blood urea nitrogen than patients consuming the SEF supplement. Consumption of the NEF supplement was also associated with significantly reduced hospitalizations during the 3- to 6-mo evaluation period (p = 0.02). The NEF supplement was well tolerated and did not result in untoward clinical effects. These data suggest that supplemental use of an NEF provides superior nutritional management compared with an SEF for patients with early-stage HIV infection.

Endophytic bacteria from roots and crude seed extracts of a Cu-tolerant population of Agrostis capillaris were inoculated to a sunflower metal-tolerant mutant line, and their influence on Cu tolerance and phytoextraction was assessed using a Cu-contaminated soil series. Ten endophytic bacterial strains isolated from surface-sterilized A. capillaris roots were mixed to prepare the root endophyte inoculant (RE). In parallel, surface-sterilized seeds of A. capillaris were crushed in MgSO4 to prepare a crude seed extract containing seed endophytes (SE). An aliquot of this seed extract was filtered at 0.2 μm to obtain a bacterial cell-free seed extract (SEF). After surface sterilization, germinated sunflower seeds were separately treated with one of five modalities: no treatment (C), immersion in MgSO4 (CMg) or SEF solutions and inoculation with RE or SE. All plants were cultivated on a Cu-contaminated soil series (13-1020 mg Cu kg(-1)). Cultivable RE strains were mostly members of the Pseudomonas genera, and one strain was closely related to Labrys sp. The cultivable SE strains belonged mainly to the Bacillus genera and some members of the Rhodococcus genera. The treatment effects depended on the soil Cu concentration. Both SE and SEF plants had a higher Cu tolerance in the 13-517 mg Cu kg(-1) soil range as reflected by increased shoot and root DW yields compared to control plants. This was accompanied by a slight decrease in shoot Cu concentration and increase in root Cu concentration. Shoot and root DW yields were more promoted by SE than SEF in the 13-114 mg Cu kg(-1) soil range, which could reflect the influence of seed-located bacterial endophytes. At intermediate soil Cu (416-818 mg Cu kg(-1) soil), the RE and CMg plants had lower shoot Cu concentrations than the control, SE and SEF plants. At high total soil Cu (617-1020 mg Cu kg(-1)), root DW yield of RE plants slightly increased and their root Cu concentration rose by up to 1.9-fold. In terms of phytoextraction efficiency, shoot Cu removal was increased for sunflower plants inoculated with crude and bacterial cell-free seed extracts by 1.3- to 2.2-fold in the 13-416 mg Cu kg(-1) soil range. Such increase was mainly driven by an enhanced shoot DW yield. The number and distribution of endophytic bacteria in the harvested sunflower tissues must be further examined.

We experimentally demonstrate a label-free biosensor for the ERBB2 cancer gene DNA target based on the distance-dependent detection of surface-enhanced fluorescence (SEF) on nanoporous gold disk (NPGD) plasmonic nanoparticles. We achieve detection of 2.4 zeptomole of DNA target on the NPGD substrate with an upper concentration detection limit of 1 nM. Without the use of molecular spacers, the NPGD substrate as an SEF platform was shown to provide higher net fluorescence for visible and NIR fluorophores compared to glass and non-porous gold substrates. The enhanced fluorescence signals in patterned nanoporous gold nanoparticles make NPGD a viable material for further reducing detection limits for biomolecular targets used in clinical assays. With patterned nanoporous gold disk (NPGD) plasmonic nanoparticles, a label-free biosensor that makes use of distance-dependent detection of surface-enhanced fluorescence (SEF) is constructed and tested for zeptomole detection of ERBB2 cancer gene DNA targets.

OBJECTIVE

Prospective evaluation of salivary gland preservation, overall survival and local recurrence-free survival after head and neck cancer treated by helical tomotherapy (HT).

METHODS

From March 2007 to February 2009, 30 patients with head and neck cancer were treated by HT. The salivary excretion fraction (SEF) was assessed by technetium salivary gland scintigraphy before, and 6, 12 and 18 months after HT to define salivary gland preservation rates. Patients were reviewed every 3 months to assess clinical toxicity.

RESULTS

The median follow-up was 4.3 years. The mean dose to the ipsilateral parotid gland (IPG) was 25.4Gy. Good preservation of parotid gland function was observed in 84% of the 19 patients evaluated by scintigraphy at 18 months. The 5-year local recurrence-free survival (LRFS) was 100% among the 6 patients who received a dose of more than 26Gy to the parotid gland. The 28-month LRFS was 33% in the group that received a dose of less than 20Gy versus 91% in the group that received a dose of more than 20Gy to the IPG.

CONCLUSIONS

Helical tomotherapy reduced the incidence and severity of xerostomia. A mean dose to the parotid between 20 and 26Gy allowed preservation of salivary function without compromising treatment efficacy. However, parotid-sparing HT requiring a mean dose less than 20Gy is associated with an increased risk of recurrence.

OBJECTIVE

The aim of the study was to investigate the functional differences between N20m and P30m components of somatosensory-evoked magnetic cortical field (SEF) in young and senior subjects.

METHODS

Twenty-nine healthy subjects, 13 younger (mean age: 21.8years) and 16 senior (63.8 years), participated. Magnetic fields were measured using a 160-channel, whole head MEG. Single- and paired-pulse stimulations of 200 artifact-free MEG signal epochs were averaged separately. We calculated how aging affects recovery function of SEFs.

RESULTS

The senior showed a prolonged N20m peak latency compared to the younger, although the P30m peak latency was not significantly different between groups. The N20m ratios at 60 and 80 ms in the senior were significantly increased compared to the ratios in the younger (60 ms: P<0.05, 80 ms: P<0.001). The P30m ratios at inter-stimulus interval (ISI) of 80 and 100 ms showed even disinhibition in the senior than in the younger (P<0.05). The younger also showed a significantly negative correlation between P30m and N20m components' recovery curves (R=0.72, P<0.05).

CONCLUSIONS

Aging-related changes that occurred in recovery functioning were the decrease in N20m component suppression and the increase in P30m component recovery, indicating that the N20m and P30m components have different functions in aging-related recovery changes.

CONCLUSIONS

Our results show that the N20m ratio at an ISI of 80 ms was significantly increased in the senior group, indicating that the second stimulus-evoked SEF was less inhibited by the initial stimulus at this ISI, suggesting less refractory effect or increased disinhibition.

FGFRL1 is a member of the fibroblast growth factor receptor family. It plays an essential role during branching morphogenesis of the metanephric kidneys, as mice with a targeted deletion of the Fgfrl1 gene show severe kidney dysplasia. Here we used the yeast two-hybrid system to demonstrate that FGFRL1 binds with its C-terminal, histidine-rich domain to Spred1 and to other proteins of the Sprouty/Spred family. Members of this family are known to act as negative regulators of the Ras/Raf/Erk signaling pathway. Truncation experiments further showed that FGFRL1 interacts with the SPR domain of Spred1, a domain that is shared by all members of the Sprouty/Spred family. The interaction could be verified by coprecipitation of the interaction partners from solution and by codistribution at the cell membrane of COS1 and HEK293 cells. Interestingly, Spred1 increased the retention time of FGFRL1 at the plasma membrane where the receptor might interact with ligands. FGFRL1 and members of the Sprouty/Spred family belong to the FGF synexpression group, which also includes FGF3, FGF8, Sef and Isthmin. It is conceivable that FGFRL1, Sef and some Sprouty/Spred proteins work in concert to control growth factor signaling during branching morphogenesis of the kidneys and other organs.

Sclerosing epithelioid fibrosarcoma (SEF) was first described in 1995 and since then 39 cases have been reported. Here we describe 6 cases of SEF (3 in women and 3 in men). The patients aged from 22 to 79 years. The tumours were located in soft tissues of the extremities (in 3 cases in the lower, in 2 instances in the upper extremity) and of the trunk (in 1 case). The lesions were partially nodular, of gray-white colour, and hard in consistency. Histologically, they were composed of epithelioid round to ovoid small cells with a sparse cytoplasm and a very low mitotic activity. The tumour cells formed cords and alveoli or were scattered individually within a dense hyalinized collagenous stroma. The neoplasms also contained foci of conventional fibrosarcoma, necrosis, calcification, and metaplastic bone. On immunohistochemistry, the neoplastic cells were positive for vimentin. Two cases were immunoreactive for epithelial membrane antigen and one tumour also for cytokeratins. The proliferative activity, assessed by MIB 1 antibody (Ki-67), was detected in 1-6% of neoplastic cells in primary tumours. Follow-up information was available in 5 patients. In two cases, there were local recurrences and distant metastases (in the lungs, upper extremity, and mediastinum). One of these patients died of SEF. The differential diagnosis of this relatively low-grade fibrosarcoma is broad and includes, along with a variety of benign and malignant soft tissue lesions, infiltrating carcinoma, and, to a lesser extent, sclerosing lymphoma.

OBJECTIVE

Cerebral arterial gas embolism (CAGE) is a serious hazard in cardiovascular surgery and other invasive procedures. We used a swine model of CAGE to determine if quantitative electroencephalography (qEEG) is a useful tool in diagnosis and prognostication of CAGE.

METHODS

0.05 ml/kg of air was injected into the ascending pharyngeal artery in 16 pigs. Intracranial pressure, lactate in brain microdialysate and brain oxygen tension were measured during 4h after embolization. The qEEG parameters mean amplitude (MAMP), alpha-delta ratio (ADR), spectral edge frequency (SEF(90)), spatial brain symmetry index (sBSI) and temporal brain symmetry index (tBSI) were calculated.

RESULTS

MAMP and tBSI but not ADR, SEF(90) and sBSI correlate with intracranial pressure, brain lactate and brain oxygen tension after 4h. Early levels of MAMP and tBSI can predict intracranial pressure, brain lactate and brain oxygen tension after 4h.

CONCLUSIONS

MAMP and tBSI are sensitive for cerebral injury and can predict outcome in a swine model of CAGE.

CONCLUSIONS

This study provides evidence for the utility of qEEG for diagnosis and prognosis in CAGE. Further studies are necessary to investigate the use of this method in patients.

Acetylcholine (ACh) is a potent neuromodulator in the brain with multiple, complex effects on neuronal function, most of which are mediated by muscarinic receptors. Generally, the most significant effect is excitation of pyramidal neurones and facilitation of responses to afferent stimulation. Much of the information on the ACh effects comes from studies utilizing in vitro or anesthetized in vivo preparations, while fewer data are available from awake animals or humans. We studied human somatosensory evoked magnetic fields (SEFs), which reflect summated postsynaptic currents in pyramidal neurones in area 3b, and in the opercular somatosensory cortex, when cholinergic transmission was modulated either by a central (scopolamine, 0.3 mg, i.v.) or peripheral (glycopyrrolate, 0.2 mg, i.v.) muscarinic antagonist. A randomized, double-blind, cross-over design was employed. SEFs were elicited by right median nerve stimulation at the wrist with constant-current pulses above motor threshold. The first excitatory cortical response from area 3b (N20m) was not affected by the central muscarinic blockade, while later P35m and P60m deflections were significantly reduced. The responses from the opercular somatosensory cortex showed some tendency toward reduction, but no significant alterations. The results show that somatosensory cortical processing can be modulated by muscarinic transmission at a relatively early stage. Relative membrane hyperpolarization of pyramidal neurons due to scopolamine (caused by blocking an ACh-induced tonic depolarization) is discussed as a possible mechanism underlying the observed effects.

OBJECTIVE

To determine whether etomidate-based induction can provide better hemodynamics than a standard thiopental sodium-based anesthetic induction.

METHODS

Prospective, single-blind clinical trial.

METHODS

Multicenter university neurosurgical operating room.

METHODS

66 ASA physical status II and III inpatients undergoing neurosurgical procedures for intracranial tumor or other pathology.

METHODS

Patients were divided into two groups for anesthetic induction. The first group (control) was divided into two subgroups, with the first subgroup receiving "low-dose" etomidate (LET) 0.4 to 0.6 mg/kg titrated to an electroencephalographic (EEG) spectral edge frequency (SEF) of 10 to 12 Hz. The second subgroup received thiopental sodium (THIO) 3 to 6 mg/kg titrated to the same EEG endpoint. The study group was given high-dose etomidate (HET) 0.5 to 1.7 mg/kg titrated to an early burst suppression pattern.

RESULTS

Baseline (awake) measurements of mean arterial pressure (MAP) heart rate (HR), and SEF were obtained prior to anesthetic induction that was accomplished using a small bolus plus an infusion of the induction drug titrated to the EEG target. MAP, HR, and SEF were recorded just prior to laryngoscopy and intubation (T1), 30 seconds after laryngoscopy and intubation (T2), and 90 seconds after (T3) laryngoscopy and intubation. Times to reach EEG endpoint, along with total dose of anesthetic given, were also recorded. Compared with baseline values, the THIO group had the highest increase in both HR (22.9 +/- 4.4 bpm.) and MAP (16.8 +/- 4.2 mmHg) (P < 0.05) after laryngoscopy and intubation. The LET group also had significant increases compared with the HET group that demonstrated the least hemodynamic variability. No correlations could be made between age and dose of induction drug.

CONCLUSIONS

Etomidate-based anesthetic induction, titrated to EEG burst suppression, produced stable hemodynamics during laryngoscopy and intubation as compared with lower dose, more "classic" inductions with etomidate or thiopental.