Combined voltage and calcium epifluorescence imaging in vitro and in vivo reveals subthreshold and suprathreshold dynamics of mouse barrel cortex

Cortical dynamics can be imaged at high spatiotemporal resolution with voltage-sensitive dyes (VSDs) and calcium-sensitive dyes (CaSDs). We combined these two imaging techniques using epifluorescence optics together with whole cell recordings to measure the spatiotemporal dynamics of activity in the mouse somatosensory barrel cortex in vitro and in the supragranular layers in vivo. The two optical signals reported distinct aspects of cortical function. VSD fluorescence varied linearly with membrane potential and was dominated by subthreshold postsynaptic potentials, whereas the CaSD signal predominantly reflected local action potential firing. Combining VSDs and CaSDs allowed us to monitor the synaptic drive and the spiking activity of a given area at the same time in the same preparation. The spatial extent of the two dye signals was different, with VSD signals spreading further than CaSD signals, reflecting broad subthreshold and narrow suprathreshold receptive fields. Importantly, the signals from the dyes were differentially affected by pharmacological manipulations, stimulation strength, and depth of isoflurane anesthesia. Combined VSD and CaSD measurements can therefore be used to specify the temporal and spatial relationships between subthreshold and suprathreshold activity of the neocortex.

Fiberoptic system for recording dendritic calcium signals in layer 5 neocortical pyramidal cells in freely moving rats

Calcium influx into the dendritic tufts of layer 5 neocortical pyramidal neurons modifies a number of important cellular mechanisms. It can trigger local synaptic plasticity and switch the firing properties from regular to burst firing. Due to methodological limitations, our knowledge about Ca2+ spikes in the dendritic tuft stems mostly from in vitro experiments. However, it has been speculated that regenerative Ca2+ events in the distal dendrites correlate with distinct behavioral states. Therefore it would be most desirable to be able to record these Ca2+ events in vivo, preferably in the behaving animal. Here, we present a novel approach for recording Ca2+ signals in the dendrites of populations of layer 5 pyramidal neurons in vivo, which ensures that all recorded fluorescence changes are due to intracellular Ca2+ signals in the apical dendrites. The method has two main features: 1) bolus loading of layer 5 with a membrane-permeant Ca2+ dye resulting in specific loading of pyramidal cell dendrites in the upper layers and 2) a fiberoptic cable attached to a gradient index lens and a prism reflecting light horizontally at 90 degrees to the angle of the apical dendrites. We demonstrate that the in vivo signal-to-noise ratio recorded with this relatively inexpensive and easy-to-implement fiberoptic-based device is comparable to conventional camera-based imaging systems used in vitro. In addition, the device is flexible and lightweight and can be used for recording Ca2+ signals in the distal dendritic tuft of freely behaving animals.

An open-label, noncomparative phase II trial to evaluate the efficacy and safety of docetaxel in combination with gefitinib in patients with hormone-refractory metastatic prostate cancer

BACKGROUND: Prostate cancer is the most common type of cancer in men, however, therapeutic options are limited. 50-90% of hormone-refractory prostate cancer cells show an overexpression of epidermal growth factor receptor (EGFR), which may contribute to uncontrolled proliferation and resistance to chemotherapy. In vitro, gefitinib, an orally administered tyrosine kinase inhibitor, has shown a significant increase in antitumor activity when combined with chemotherapy. PATIENTS AND METHODS: In this phase II study, the safety and efficacy of gefitinib in combination with docetaxel, a chemotherapeutic agent commonly used for prostate cancer, was investigated in patients with hormone-refractory prostate cancer (HRPC). 37 patients with HRPC were treated continuously with gefitinib 250 mg once daily and docetaxel 35 mg/m2 i.v. for up to 6 cycles. PSA response, defined as a =50% decrease in serum PSA compared with trial entry, was the primary efficacy parameter. PSA levels were measured at prescribed intervals. RESULTS: The response rate and duration of response were consistent with those seen with docetaxel monotherapy. The combination of docetaxel and gefitinib was reasonably well tolerated in this study. CONCLUSION: Future studies should investigate whether patients with specific tumor characteristics, e.g. EGFR protein overexpression, respond better to gefitinib than patients without, leading to a more customized therapy option.

Human alveolar echinococcosis after fox population increase, Switzerland

We analyzed databases spanning 50 years, which included retrospective alveolar echinococcosis (AE) case finding studies and databases of the 3 major centers for treatment of AE in Switzerland. A total of 494 cases were recorded. Annual incidence of AE per 100,000 population increased from 0.12-0.15 during 1956-1992 and a mean of 0.10 during 1993-2000 to a mean of 0.26 during 2001-2005. Because the clinical stage of the disease did not change between observation periods, this increase cannot be explained by improved diagnosis. Swiss hunting statistics suggested that the fox population increased 4-fold from 1980 through 1995 and has persisted at these higher levels. Because the period between infection and development of clinical disease is long, the increase in the fox population and high Echinococcus multilocularis prevalence rates in foxes in rural and urban areas may have resulted in an emerging epidemic of AE 10-15 years later.

Hepatoblastoma with a low serum alpha-fetoprotein level at diagnosis: The SIOPEL group experience

AIM OF THE STUDY: To investigate the characteristics of patients with hepatoblastoma and low serum alpha-fetoprotein (AFP) at diagnosis. PATIENTS AND METHODS: Inclusion of all 21 patients accrued onto SIOPEL trials, whose serum AFP was <100ng/ml at diagnosis. Slides of all 15 patients with available histological material were centrally reviewed. RESULTS: Median age: 10 months. Disease extension at diagnosis: PRETEXT group: II (3 patients), III (10 patients) and IV (8 patients). Extra-hepatic extension: 8 patients. Multifocal tumour: 8 patients. Histology at review: wholly epithelial subtype: 11/15 patients including nine with a small-cell undifferentiated histology. Outcome: only 9 patients achieved a partial response and 16 died. Median survival: 4.4 months. Two-year overall survival: 24% (confidence interval 10-45%). CONCLUSION: This study clearly identifies patients with hepatoblastoma and low serum AFP at diagnosis as a high-risk subgroup with extensive disease at diagnosis, poor response to chemotherapy and a poor outcome.

Human temporal bones versus mechanical model to evaluate three middle ear transducers

A life-size mechanical middle ear model and human temporal bones were used to evaluate three different middle ear transducers for implantable hearing aids: the driving rod transducer (DRT), the floating mass transducer (FMT) or vibrant sound bridge, and the contactless transducer (CLT). Results of the experiments with the mechanical model were within the range of the results for human temporal bones. However, results with the mechanical model showed better reproducibility. The handling of the mechanical model was considerably simpler and less time-consuming. Systematic variations of mounting parameters showed that the angle of the rod has virtually no effect on the output of the DRT, the mass loading on the cable of the FMT has a larger impact on the output than does the tightness of crimping, and the output level of the CLT can be increased by 10 dB by optimizing the mounting parameters.

Speech understanding in quiet and in noise with the bone-anchored hearing aids Baha Compact and Baha Divino

CONCLUSIONS: Speech understanding is better with the Baha Divino than with the Baha Compact in competing noise from the rear. No difference was found for speech understanding in quiet. Subjectively, overall sound quality and speech understanding were rated better for the Baha Divino. OBJECTIVES: To compare speech understanding in quiet and in noise and subjective ratings for two different bone-anchored hearing aids: the recently developed Baha Divino and the Baha Compact. PATIENTS AND METHODS: Seven adults with bilateral conductive or mixed hearing losses who were users of a bone-anchored hearing aid were tested with the Baha Compact in quiet and in noise. Tests were repeated after 3 months of use with the Baha Divino. RESULTS: There was no significant difference between the two types of Baha for speech understanding in quiet when tested with German numbers and monosyllabic words at presentation levels between 50 and 80 dB. For speech understanding in noise, an advantage of 2.3 dB for the Baha Divino vs the Baha Compact was found, if noise was emitted from a loudspeaker to the rear of the listener and the directional microphone noise reduction system was activated. Subjectively, the Baha Divino was rated statistically significantly better in terms of overall sound quality.

Impact of a self-developed planning and self-constructed navigation system on skull base surgery: 10 years experience

CONCLUSION: Our self-developed planning and navigation system has proven its capacity for accurate surgery on the anterior and lateral skull base. With the incorporation of augmented reality, image-guided surgery will evolve into 'information-guided surgery'. OBJECTIVE: Microscopic or endoscopic skull base surgery is technically demanding and its outcome has a great impact on a patient's quality of life. The goal of the project was aimed at developing and evaluating enabling navigation surgery tools for simulation, planning, training, education, and performance. This clinically applied technological research was complemented by a series of patients (n=406) who were treated by anterior and lateral skull base procedures between 1997 and 2006. MATERIALS AND METHODS: Optical tracking technology was used for positional sensing of instruments. A newly designed dynamic reference base with specific registration techniques using fine needle pointer or ultrasound enables the surgeon to work with a target error of < 1 mm. An automatic registration assessment method, which provides the user with a color-coded fused representation of CT and MR images, indicates to the surgeon the location and extent of registration (in)accuracy. Integration of a small tracker camera mounted directly on the microscope permits an advantageous ergonomic way of working in the operating room. Additionally, guidance information (augmented reality) from multimodal datasets (CT, MRI, angiography) can be overlaid directly onto the surgical microscope view. The virtual simulator as a training tool in endonasal and otological skull base surgery provides an understanding of the anatomy as well as preoperative practice using real patient data. RESULTS: Using our navigation system, no major complications occurred in spite of the fact that the series included difficult skull base procedures. An improved quality in the surgical outcome was identified compared with our control group without navigation and compared with the literature. The surgical time consumption was reduced and more minimally invasive approaches were possible. According to the participants' questionnaires, the educational effect of the virtual simulator in our residency program received a high ranking.

Echinococcosis presenting as an otogenic brain abscess: an unusual lesion of the middle ear cleft and temporal lobe

This paper presents a case of a 28-year-old male with a seizure episode and a 4-year history of intermittent tinnitus on the left ear. On computed tomography and magnetic resonance imaging, a density with rim enhancement was found at the temporal lobe, associated with mastoid tegmen destruction and middle ear mass, indicating cholesteatoma with complicating brain abscess. Evacuation of the brain abscess was performed with a combined otolaryngologic and neurosurgical procedures (canal wall-down mastoidectomy and temporal craniotomy). The pathology turned out to be infestation with Echinococcus granulosus.

Benign paroxysmal positional vertigo in mountain bikers

We evaluated 4 men who had benign paroxysmal positional vertigo (BPPV) that occured several hours after intensive mountain biking but without head trauma. The positional maneuvers in the planes of the posterior and horizontal canals elicited BPPV, as well as transitory nystagmus. This was attributed to both the posterior and horizontal semicircular canals (SCCs) on the left side in 1 patient, in these 2 SCCs on the right side in another patient, and to the right posterior SCC in the other 2 patients. The symptoms disappeared after physiotherapeutic maneuvers in 2 patients and spontaneously in the other 2 patients. Cross-country or downhill mountain biking generates frequent vibratory impacts, which are only partially filtered through the suspension fork and the upper parts of the body. Biomechanically, during a moderate jump, before landing, the head is subjected to an acceleration close to negative 1 g, and during impact it is subjected to an upward acceleration of more than 2g. Repeated acceleration-deceleration events during intensive off-road biking might generate displacement and/or dislocation of otoconia from the otolithic organs, inducing the typical symptoms of BPPV. This new cause of posttraumatic BPPV should be considered as an injury of minor severity attributed to the practice of mountain biking.

An interfering Go/No-go task does not affect accuracy in a Concealed Information Test

Following the idea that response inhibition processes play a central role in concealing information, the present study investigated the influence of a Go/No-go task as an interfering mental activity, performed parallel to the Concealed Information Test (CIT), on the detectability of concealed information. 40 undergraduate students participated in a mock-crime experiment and simultaneously performed a CIT and a Go/No-go task. Electrodermal activity (EDA), respiration line length (RLL), heart rate (HR) and finger pulse waveform length (FPWL) were registered. Reaction times were recorded as behavioral measures in the Go/No-go task as well as in the CIT. As a within-subject control condition, the CIT was also applied without an additional task. The parallel task did not influence the mean differences of the physiological measures of the mock-crime-related probe and the irrelevant items. This finding might possibly be due to the fact that the applied parallel task induced a tonic rather than a phasic mental activity, which did not influence differential responding to CIT items. No physiological evidence for an interaction between the parallel task and sub-processes of deception (e.g. inhibition) was found. Subjects' performance in the Go/No-go parallel task did not contribute to the detection of concealed information. Generalizability needs further investigations of different variations of the parallel task.