Gaze-evoked involuntary movements

Voluntary gaze may evoke a number of neurological phenomena such as vertigo, tinnitus, blepharoclonus, eyelid nystagmus, "facial nystagmus," involuntary laughter, and seizures. We report two patients in whom eccentric gaze evoked facial twitching and arm movement. Electroencephalograms remained unchanged during these movements. The pathogenesis of these movements is unclear but may involve ephaptic transmission.     

Involvement of nitric oxide synthase in the physiology and pathophysiology of facial nerve function and dysfunction

To date few reports have discussed the presence and function of nitric oxide (NO) in structures of the facial nerve. We performed nicotinamide adenine dinucleotide phosphate (NADPH-d)-diaphorase-histochemistry and immunohistochemistry on the intratemporal portion of the facial nerve, including the geniculate ganglion, of guinea pigs using specific antibodies to the three known isoforms of NO synthase and soluble guanylyl-cyclase (sGC). Normal facial nerves were compared to those treated intratympanically with bacterial lipopolysaccharides (LPS) and tumor necrosis factor-α (TNF-α). Both constitutive NOS isoforms and sGC could be detected in the bipolar ganglion cells of normal animals, while the inducible isoform (iNOS or NOS II) was not found. Endothelial NOS (NOS III) and sGC were present in blood vessels and were predominantly found in the perineurial sheath and less in the endoneurium. sGC could be detected in all fibers in a cross section of the facial nerve. LPS and TNF treatment led to the detection of iNOS in the perikaryia of the geniculate ganglion and the perineural sheath. These findings imply that NO may be involved in neurotransmission at least in the visceroafferent system. NO regulates vascular tone of nutrient blood vessels in the perineural sheath and endoneurium. The presence of sGC indicates that NO acts via its second messenger cGMP. NOS II expression may be a contributing factor to facial nerve palsy via two different mechanisms: NOS II-generated NO may lead to an overstimulation of the visceroefferent nerve fibers and motor fibers of the facial nerve. Dysregulation in facial nerve blood vessels could lead to edema and elevated pressure on the nerve within its osseous canal. Received: 13 April 1999 / Accepted: 12 August 1999     

The delivery of aerosolized steroids from MDIs with nozzle extensions: Quantitative laboratory evaluation of a method to improve aerosol delivery to intubated patients

Objective Pulmonary deposition of aerosolized drug from a metered dose inhaler (MDI) is low with intubated patients. In the laboratory, extension of the MDI nozzle to the endotracheal tube tip has been shown to increase the delivered dose of albuterol. The objectives of this study were to determine the dose of aerosolized steroid (beclomethasone and triamcinolone) delivered through a MDI nozzle extension, the effect of nozzle extension length and number of actuations on the delivered dose, and particle size delivered through the nozzle extension.Design A 19-G catheter was used as the MDI nozzle extension. The nozzle extension was attached to a 60-ml syringe via the Luer-Lok connection, and the distal end was directed through a hole drilled into a 15-ml capped tube. The MDI was placed into the syringe and actuated by pressing the syringe plunger. Drug delivered through the nozzle extension into the tube was dissolved in methanol (beclomethasone) or ethanol (triamcinolone). Nozzle extension lengths of 10 cm, 20 cm and 30 cm were studied. For each nozzle extension length, delivery was assessed using one, two, three and five actuations of each drug. Drug remaining in the nozzle extension was recovered by rinsing with the appropriate solvent. Aerosol particle size leaving the nozzle extension was determined using a seven-stage cascade impactor. Beclomethasone and triamcinolone concentrations were determined by spectrophotometry at 239 nm.Setting Respiratory care laboratory of a university teaching hospital.Results For the pooled results, 70.2±14.1% of the dose was delivered through the nozzle extension, with no difference between beclomethasone and triamcinolone (p=0.838). The proportion of drug delivered through the 10-cm extension (76.7±8.4%) was greater than that from the 20-cm (66.1±16.5%) and 30-cm (67.7±13.9%) extensions (p=0.001). Less drug was delivered through the extension with one actuation (54.1±17.7%) than with two (71.2±7.7%), three (77.2±5.5%), or five actuations (78.2±4.3%) (p<0.001). There was a decrease in MMAD with increasing nozzle extension length (3.14±0.61 m for 10 cm, 2.97±0.28 m for 20 cm, 2.37±0.27 m for 30 cm;p=0.005).Conclusions A high proportion of aerosolized steroid was delivered with a MDI actuated through a nozzle extension. The proportion delivered through the nozzle extension was significantly less with longer nozzle extensions and with fewer actuations, but this may not be clinically important. Although particle sizes were smaller from longer nozzle extensions, all were within the respirable range. These results suggest that steroids can be delivered efficiently using a MDI nozzle extension.Presented in part at the 1994 International Conference, ALA/ATS, in Boston, MA, May 23, 1994Work completed in the Respiratory Care Laboratory and Henry K. Beecher Anesthesia Laboratory, Massachusetts General Hospital, Boston, MA. Supported in part by the Puritan-Bennett Corporation and the American Respiratory Care Foundation     

P53 alterations show significant correlation with gene amplification and s-phase index in breast-cancer

Correlation of p53 gene/protein alterations with incidence of oncogene amplification, a potential marker of prognosis, was evaluated in 26 fresh breast cancer samples. p53 gene was analyzed by SSCP and DNA sequencing while p53 protein status was investigated by immunohistochemistry (IH). Amplification of c-erbB2/neu, c-myc, N-ras, int-2, hst, PRAD-1 and EGFR genes was studied by slot blot and in situ hybridizations. p53 alterations were found in 31% cases by SSCP and 42% by IH; gene amplification was detected in 27% cases. p53 gene alterations correlated significantly with gene amplification (p=0.006) and also with higher S-phase index (p=0.026), aneuploidy (p=0.026) and negative progesterone receptor status (p=0.043).     

Soybean isoflavones, genistein and genistin, inhibit rat myoblast proliferation, fusion and myotube protein synthesis.

The isoflavones, genistein and genistin, are cytotoxic in vitro (e.g. , inhibition of cell proliferation), due in part to inhibition of protein tyrosine kinase and DNA topoisomerase activities. Normal cell functions associated with these enzymatic activities could potentially be impaired in animals through ingestion of soybean products. In this study, cultured rat myogenic cells (L8) were used to determine whether genistein or genistin influences myoblast proliferation and fusion, and myotube protein synthesis and degradation. Genistein or genistin was dissolved in dimethylsulfoxide and included in the culture medium at 0, 1, 10 or 100 micromol/L. Myoblast proliferation was measured by methyl-3H-thymidine incorporation over 48 h. Myoblast differentiation was evaluated by the number of nuclei in multinucleated myotubes. Myotube protein synthesis was measured by 2-h 3H-amino acid incorporation into the myosin and total protein pools after acute (2 h) or chronic (24 h) exposure to similar treatments; protein degradation was measured by measuring radioactivity in protein pools following a time course of protein breakdown after myotube proteins were prelabeled with 3H-amino acids. Genistein or genistin strongly inhibited in vitro myoblast proliferation (P < 0.001) and fusion (P < 0.001) in a dose-dependent manner with effective genistein concentration as low as 1 micromol/L. Genistein or genistin inhibited protein accretion in myotubes (P < 0.001). Decreased protein accretion is largely a result of inhibition on cellular (myofibrillar) protein synthesis rate. No adverse effect on protein degradation was observed. Results suggest that if sufficient circulating concentrations are reached in tissues of animals consuming soy products, genistein/genistin can potentially affect normal muscle growth and development.     

Improvement of rat lung structure and function after preservation with celsior

Ischemia/reperfusion-induced increase in pulmonary microvascular permeability was shown to be reduced after preservation with Celsior. We investigated reimplantation-induced lung injury in isolated, reperfused rat lungs after preservation via the pulmonary artery with Celsior, Celsior + prostacyclin, and reduced-potassium (40 mmol) Euro-Collins solution (40 ml/kg/body wt each) followed by 2 h of cold ischemia. Arterial and veneous oxygen tensions were recorded during 50 min of in vitro reperfusion after which the lungs (10 right lungs per experimental group) were fixed by vascular perfusion. The tissue was further processed for microscopy, and histological changes were quantified stereologically. Lung preservation with Celsior resulted in a significantly higher volume of air-filled alveolar space with a large proportion of widely distended alveoli compared with the other groups. In the Euro-Collins group the fraction of atelectatic alveoli exceeded that observed in Celsior-preserved lungs. In accordance, the difference between arterial and venous oxygen tensions was significant among Euro-Collins- and Celsior-protected lungs, with improved oxygenation values in the Celsior group. In contrast, addition of prostacyclin to Celsior treatment resulted in rather variable structural as well as functional data. There were no differences in the volumes of intraalveolar edema among the groups tested. However, the volume of alveolar tissue was increased in the Euro-Collins group. In conclusion, compared with Euro-Collins and Celsior + prostacyclin solutions, preservation with Celsior resulted in improved structural characteristics which in combination with improved oxygenation parameters supports the prospective advantage of Celsior in clinical organ preservation.