Inducible genetic suppression of neuronal excitability.

Graded, reversible suppression of neuronal excitability represents a logical goal of therapy for epilepsy and intractable pain. To achieve such suppression, we have developed the means to transfer "electrical silencing" genes into neurons with sensitive control of transgene expression. An ecdysone-inducible promoter drives the expression of inwardly rectifying potassium channels in polycistronic adenoviral vectors. Infection of superior cervical ganglion neurons did not affect normal electrical activity but suppressed excitability after the induction of gene expression. These experiments demonstrate the feasibility of controlled ion channel expression after somatic gene transfer into neurons and serve as the prototype for a novel generalizable approach to modulate excitability.     

In Process Citation

Pure word deafness (auditory verbal agnosia) is characterized by an impairment of auditory comprehension, repetition of verbal material and writing to dictation whereas spontaneous speech production and reading largely remain unaffected. Sometimes, this syndrome is preceded by complete deafness (cortical deafness) of varying duration. Perception of vowels and suprasegmental features of verbal utterances (e.g., intonation contours) seems to be less disrupted than the processing of consonants and, therefore, might mediate residual auditory functions. Often, lip reading and/or slowing of speaking rate allow within some limits to compensate for speech comprehension deficits. Apart from a few exceptions, the available reports of pure word deafness documented a bilateral temporal lesion. In these instances, as a rule, identification of nonverbal (environmental) sounds, perception of music, temporal resolution of sequential auditory cues and/or spatial localization of acoustic events were compromised as well. The observed variable constellation of auditory signs and symptoms in central hearing disorders following bilateral temporal disorders, most probably, reflects the multitude of functional maps at the level of the auditory cortices subserving, as documented in a variety of non-human species, the encoding of specific stimulus parameters each. Thus, verbal/nonverbal auditory agnosia may be considered a paradigm of distorted "auditory scene analysis" (Bregman 1990) affecting both primitive and schema-based perceptual processes. It cannot be excluded, however, that disconnection of the Wernicke-area from auditory input (Geschwind 1965) and/or an impairment of suggested "phonetic module" (Liberman 1996) contribute to the observed deficits as well. Conceivably, these latter mechanisms underly the rare cases of pure word deafness following a lesion restricted to the dominant hemisphere. Only few instances of a rather isolated disruption of the discrimination/identification of nonverbal sound sources, in the presence of uncompromised speech comprehension, have been reported so far (nonverbal auditory agnosia). As a rule, unilateral right-sided damage has been found to be the relevant lesion.     

Pulmonary Failure After Norwood Procedure: Indication for Extracorporeal Membrane Oxygenation? A Case Report

Today some authors consider univentricular repair a contraindication for postoperative cardiac extracorporeal membrane oxygenation (ECMO). The question is whether or not ECMO is indicated as pulmonary support in case of an overwhelming pulmonary infection during the postoperative course after a Norwood procedure. During the prolonged weaning period after a Norwood procedure using a 4 mm aortopulmonary shunt, proven respiratory syncytial virus (RSV) bronchiolitis occurred at the time of expected weaning from artificial ventilation. Venovenous ECMO was able to improve oxygenation, but when pulmonary opacification failed to resolve, ECMO was terminated after 12 days.     

Aortopulmonary collateral artery embolization during postoperative extracorporeal membrane oxygenation after arterial switch procedure

Aortopulmonary collateral arteries sometimes complicate cyanotic congenital heart defects. Combined with a relevant left-right shunt, this could result in massive airway bleeding during and after corrective surgery. A preoperatively diagnosed 1.2 mm small aortopulmonary collateral artery in a newborn suffering from transposition of the great arteries caused life-threatening airway bleeding during surgery. Postoperative extracorporeal membrane oxygenation (ECMO) was necessary, and coil embolization was performed on ECMO to terminate pulmonary bleeding.     

Acute clinical deterioration in a patient with end-stage dilated cardiomyopathy and left ventricular thrombus formation

The case of a 17-year-old male patient with severe end-stage dilated cardiomyopathy and a large thrombus formation within the cavum of the left ventricle is reported. After an acute thrombectomia combined with a partial left ventriculectomy (Batista procedure), the patient was successfully treated with an appropriate left ventricular assist device (LVAD) system using a centrifugal nonocclusive pump (Biomedicus, Medtronic, Anaheim, CA, U.S.A.). Mechanical support was removed on Day 9, and the patient was discharged from the hospital on Day 19. The effectiveness of emergency mechanical support in patients with very unfavorable prognoses is discussed.     

What do we know about the reliability and validity of physical examination tests used to examine the upper extremity?

The literature regarding the reliability and validity of commonly used clinical tests for disorders of the upper extremity was reviewed. Formal literature search, standard texts, and experts in the field of upper extremity were consulted to locate relevant articles. Range of motion and strength testing of the upper limb have been shown to be reliable, while various tests used for the diagnosis of conditions in the upper limb, such as carpal tunnel syndrome and rotator cuff tendinopathy, have been shown to have varying degrees of validity. Overall, however, we determined that there is little evidence regarding the reliability and validity of physical examination for the upper extremity and specifically less information available regarding the reliability of diagnostic physical examination tests and the validity of impairment measures used for the upper limb. Further studies in this area are warranted in view of the impact of these findings on the treatment of patients.     

Successful placement and re-expansion of a new balloon expandable stent to maintain patency of the ductus arteriosus in a newborn animal model

Objective: We performed this study in order to evaluate the usefulness of a new balloon expandable stent for maintaining ductal patency in a neonatal piglet model and to evaluate the ability to re-expand the stent weeks following initial implantation. Background: Maintaining patency of the ductus arteriosus without administration of Prostaglandin E has been reported previously using balloon dilation and stent implantation techniques. However, the experience is limited and the currently available stents are not modified for neonates. Methods: 14 newborn piglets all at age 12 days and median weight 3.6 Kg (range 2.7-4.3 Kg), underwent initial balloon dilation of the ductus arteriosus. Angiography after dilation demonstrated no significant left to right shunt. All piglets underwent successful stent (3.5 mm x 17 mm) placement in the ductus arteriosus. Results: Percutaneous ductal stent implantation via the arterial route was successful in all piglets with angiographic demonstration of a significant left to right shunt. Follow-up studies at weekly intervals with color flow Doppler were used to confirm patency of the stents. In 3 piglets the stent was not patent at initial follow-up and autopsy revealed sub-optimal stent placement. In two animals the stent was later re-expanded to 4 mm at 22 days, in one to 4 mm at 30 days and in one to 6 mm at 15 days, maintaining flow for an additional period of 15 to 34 days.(ABSTRACT TRUNCATED AT 250 WORDS)     

Exceptional performance in heart preservation with an amino acid—Containing perfusion fluid

This is a report of a study aimed at putting into practice a new theory for hypothermic preservation of viable organs. A perfusion fluid elaborated according to this theory was applied in preservation of the heart, and resulted in storage of the heart for up to 72 hours with preservation of its functions (rhythm, presystolic ventricular pressure, systolic ventricular pressure, cardiac work, coronary blood pressure, sensitivity to drugs) and its morphology. An important finding was that repeated heart storage for 24 hours alternating with functional testing for 5–7 hours could be performed without irreversible alterations of cardiac function and fine structure. Furthermore, during functional testing following storage the hearts consistently demonstrated improvement of function in time, suggesting that the preserved myocardial tissues were able to rapidly achieve metabolic reequilibration. The results of this study provide the possibility of developing a system for efficient ex vivo heart conditioning before transplantation.

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Résumé Nous avons testé la valeur d'une nouvelle théorie sur la préservation d'organes en hypothermie. Un liquide de perfusion conforme à cette théorie a été utilisé pour la préservation cardiaque. Il permet de conserver le coeur pendant 72 heures, sans altérations de ses fonctions (rythme, pression ventriculaire pré-systolique et systolique, travail cardiaque, pression coronaire, sensibilité aux médicaments) ni de sa morphologie. De plus, le coeur peut-être, à plusieurs reprises, conservé pendant 24 heures, avec des intervalles de reprise fonctionnelle de 5–7 heures, sans que sa fonction ni sa structure fine ne soient altérées de façon irréversible. Enfin, l'étude fonctionnelle montre qu'après conservation la fonction cardiaque s'améliore avec le temps, suggérant donc une rééquilibration métabolique rapide du tissu myocardique. Les résultats de cette étude permettront la mise au point d'un système efficace de conservation cardiaque ex-vivo en vue de la transplantation.

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Supported by the German Heart Center, Munich, and the German Academy Department for Foreign Scientific Relationships, Bonn.     

The "preoxygenation" special function in mechanical ventilators. Medically necessary and an ergonomic plus?

Hypoxia-related cardiovascular complications and unnecessary monitor and ventilator alarms are well-known problems during tracheobronchial suctioning. Preoxygenation together with temporary muting of acoustic alarms for tracheobronchial suctioning are provided by a single operational control of the ventilator "Evita", software release 9 (Dr?gerwerk AG). This integrated function was evaluated in medical and ergonomic respects. METHODS. Thirty tracheobronchial suctioning procedures each, with or without preoxygenation, were evaluated. The subjects were patients in our anesthesiological intensive care unit who were under continuous positive-pressure ventilation with FIO2 between 0.25 and 0.6. They ranged in age from 18 months to 72 years. Each patient served as her/his own control after about 1-h delays. Depending on the preference of the nurse, the procedures were either both on-ventilator (via the catheter port) or both off-ventilator suctionings. Arterial samples for blood gas analyses as well as arterial oxygen saturation (SaO2) determinations were taken before preoxygenation, at the moment of disconnection or opening of the catheter port, at reconnection or closure of the port, and 5 min later. Moreover, the number of changes in position of the performing nurse, the number of acoustic ventilator alarms, and the duration of the procedure were recorded. Finally, assessments of the integrated ventilator feature by the 28 participating nurses were collected both as a score from 1 ("most useful and innovative") to 5 ("completely superfluous and distracting") and as detailed statements. RESULTS. Arterial blood gas results and SaO2 courses differentiated as to procedures with or without preoxygenation as well as on-ventilator and off-ventilator suctioning are shown in Table 1 (values are mean +/- standard deviation). Without preoxygenation, most patients did not exhibit threatening drops in SaO2 (values fell from 98.2%) to 97.0% on the average). Nevertheless, preoxygenation provided an additional safety margin (100% saturation throughout the procedure in all patients). Under certain conditions, e.g., low functional residual capacity as in small children or patients with adult respiratory distress syndrome (in 1 of these cases we observed a SaO2 drop to 87%), it is mandatory. Although occurring far less frequently, unnecessary acoustic alarms were not completely excluded by the integrated function because the ventilator would not recognize the insertion of the suction catheter via the catheter port as the expected disconnection. Thus, coughing was able to trigger the "high airway pressure" alarm. As expressed by an average score of 2.8, approval of the integrated ventilator function prevailed among the involved nursing staff.