Mutation analysis of the <Emphasis Type="Italic">MDM4</Emphasis>gene in German breast cancer patients

Background  

MDM4 is a negative regulator of p53 and cooperates with MDM2 in the cellular response to DNA damage. It is unknown, however, whether MDM4 gene alterations play some role in the inherited component of breast cancer susceptibility.     

Bilateral linear scleroderma "en coup de sabre" associated with facial atrophy and neurological complications

Background

Ultrasonography with 20 MHz frequency can be used to estimate tumour thickness preoperatively in malignant melanoma (MM) of the skin. The vertical invasion depth is the single most important prognostic factor for localised MM, and its preoperative knowledge would be very useful for the planning of surgical procedures. Since ultrasonographic distance measurements directly depend upon the tissue specific ultrasound velocity, we determined the ultrasound velocity in primary melanoma.

Results

Ultrasound velocity was calculated from runtime differences of a 20 MHz ultrasound signal along a known distance either through water alone or through thick specimens of primary MM. The ultrasound velocities varied between 1553 m/s and 1588 m/s with a mean of 1564 m/s in four different MM specimens. The analysis of different parts of the specimens showed that the variation of the calculated velocities was larger between different specimens than within one individual specimen.

Conclusions

The ultrasound velocity in MM tissue may be slightly lower than normally assumed, thereby explaining a part of the overestimation usually found in sonographic measurement of melanoma invasion depth. Additionally, the variation of ultrasound velocity between individual tumours may contribute to the impairment of the correlation found between sonometry and Breslow's measurement of MM invasion depth. For practical reasons, a setting of 1580 m/s will be appropriate for ultrasonography of primary malignant melanoma.     

Prioritising the prevention of medication handling errors

Objective Medication errors are frequent in a hospital setting and often caused by inappropriate drug handling. Systematic strategies for their prevention however are still lacking. We developed and applied a classification model to categorise medication handling errors and defined the urgency of correction on the basis of these findings. Setting Nurses on medical wards (including intensive and intermediate care units) of a 1,680-bed teaching hospital. Method In a prospective observational study we evaluated the prevalence of 20 predefined medication handling errors on the ward. In a concurrent questionnaire survey, we assessed the knowledge of the nurses on medication handling. The severity of errors observed in individual areas was scored considering prevalence, potential risk of an error, and the involved drug. These scores and the prevalence of corresponding knowledge deficits were used to define the urgency of preventive strategies according to a four-field decision matrix. Main outcome measure Prevalence and potential risk of medication handling errors, corresponding knowledge deficits in nurses committing the errors, and priority of quality improvement. Results In 1,376 observed processes 833 medication handling errors were detected. Errors concerning preparation (mean 0.88 errors per observed process [95% CI: 0.81–0.96], N = 645) were more frequent than administration errors (0.36 [0.32–0.41], N = 701, P < 0.001). Parenteral drugs (1.10 [1.00–1.19], N = 492) were more often involved in errors than enteral drugs (0.32 [0.28–0.36], N = 794, P < 0.001). Of the 833 observed medication errors 30.9% concerned processes of high risk, 19.0% of moderate risk, and 50.1% of low risk. Of these errors 11.4% were caused by critical dose drugs, 81.6% by uncomplicated drugs, and 6.9% by nutritional supplements or diluents without active ingredient. According to the decision matrix that also considered knowledge deficits two error types concerning enteral drugs (flaws in light protection and prescribing information) were given maximum priority for quality improvement. For parenteral drugs five errors (incompatibilities, flaws in hygiene, duration of administration, check for visible abnormalities, and again prescribing information) appeared most important. Conclusion We successfully applied a newly developed classification model to prioritise medication handling errors for prevention strategies.     

Neuronal mechanisms underlying control of a brain-computer interface

Brain-computer interfaces (BCIs) enable humans or animals to communicate or control external devices without muscle activity using electric brain signals. The BCI used here is based on self-regulation of slow cortical potentials (SCPs), a skill that most people and paralyzed patients can acquire with training periods of several hours up to months. The neurophysiological mechanisms and anatomical sources of SCPs and other event-related brain potentials have been described but the neural mechanisms underlying the self-regulation skill for the use of a BCI are unknown. To uncover the relevant areas of brain activation during regulation of SCPs, the BCI was combined with functional magnetic resonance imaging. The electroencephalogram was recorded inside the magnetic resonance imaging scanner in 12 healthy participants who learned to regulate their SCP with feedback and reinforcement. The results demonstrate activation of specific brain areas during execution of the brain regulation skill allowing a person to activate an external device; a successful positive SCP shift compared with a negative shift was closely related to an increase of the blood oxygen level-dependent response in the basal ganglia. Successful negativity was related to an increased blood oxygen level-dependent response in the thalamus compared with successful positivity. These results may indicate learned regulation of a cortico-striatal-thalamic loop modulating local excitation thresholds of cortical assemblies. The data support the assumption that human subjects learn the regulation of cortical excitation thresholds of large neuronal assemblies as a prerequisite for direct brain communication using an SCP-driven BCI. This skill depends critically on an intact and flexible interaction between the cortico-basal ganglia-thalamic circuits.     

A critical review of interfaces with the peripheral nervous system for the control of neuroprostheses and hybrid bionic systems

Considerable scientific and technological efforts have been devoted to develop neuroprostheses and hybrid bionic systems that link the human nervous system with electronic or robotic prostheses, with the main aim of restoring motor and sensory functions in disabled patients. A number of neuroprostheses use interfaces with peripheral nerves or muscles for neuromuscular stimulation and signal recording. Herein, we provide a critical overview of the peripheral interfaces available and trace their use from research to clinical application in controlling artificial and robotic prostheses. The first section reviews the different types of non-invasive and invasive electrodes, which include surface and muscular electrodes that can record EMG signals from and stimulate the underlying or implanted muscles. Extraneural electrodes, such as cuff and epineurial electrodes, provide simultaneous interface with many axons in the nerve, whereas intrafascicular, penetrating, and regenerative electrodes may contact small groups of axons within a nerve fascicle. Biological, technological, and material science issues are also reviewed relative to the problems of electrode design and tissue injury. The last section reviews different strategies for the use of information recorded from peripheral interfaces and the current state of control neuroprostheses and hybrid bionic systems.