Carbon dioxide laser vaporization of the inferior turbinate for allergic rhinitis: short-term results

Carbon dioxide laser vaporization of the turbinate has recently become accepted as a common treatment for allergic rhinitis. Usually, only a single procedure is applied to minimize trauma. However, repeated procedures on separate days are often required to achieve an adequate effect. Therefore, we attempted a new method of vaporization and evaluated the outcome, and also tried to determine which patients have good indications for laser treatment. To widely and deeply vaporize the inferior turbinate, we repeated the procedure 3 times in 1 session after removing the carbon coating from the previous vaporization under nasal endoscopic observation. After the procedure, most patients experienced complete nasal obstruction for 2 or 3 days, but there was no intraoperative or postoperative bleeding or severe pain. All patients obtained improvement of their chief complaints and were satisfied 2 months after the operation. In particular, 60% of the patients were completely relieved of refractory nasal obstruction. Most patients were more satisfied with the effects than are those treated by the usual methods. Completely successful cases (improvement in all symptoms and complete satisfaction obtained) were selected and were compared with other cases. Favorable prognostic factors are more severe complaints, longer symptomatic periods, stronger allergic reactions, and worse nasal resistance and its greater improvement with administration of decongestant nasal drops. This method may be especially accepted by patients with severe complaints, in particular nasal obstruction, who do not experience enough relief with conservative therapies or have enough time to make frequent visits to an outpatient clinic over a period of several weeks.     

Changes in Cytochemistry of Sensory and Nonsensory Cells in Gentamicin-Treated Cochleas

Effects of a single local dose of gentamicin upon sensory and nonsensory cells throughout the cochlea were assessed by changes in immunostaining patterns for a broad array of functionally important proteins. Cytochemical changes in hair cells, spiral ganglion cells, and cells of the stria vascularis, spiral ligament, and spiral limbus were found beginning 4 days post administration. The extent of changes in immunostaining varied with survival time and with cell type and was not always commensurate with the degree to which individual cell types accumulated gentamicin. Outer hair cells, types I and II fibrocytes of the spiral ligament, and fibrocytes in the spiral limbus showed marked decreases in immunostaining for a number of constituents. In contrast, inner hair cells, type III fibrocytes and root cells of the spiral ligament, cells of the stria vascularis, and interdental cells in the spiral limbus showed less dramatic decreases, and in some cases they showed increases in immunostaining. Results indicate that, in addition to damaging sensory cells, local application of gentamicin results in widespread and disparate disruptions of a variety of cochlear cell types. Only in the case of ganglion cells was it apparent that the changes in nonsensory cells were secondary to loss or damage of hair cells. These results indicate that malfunction of the ear following gentamicin treatment is widespread and far more complex than simple loss of sensory elements. The results have implications for efforts directed toward detecting, preventing, and treating toxic effects of aminoglycosides upon the inner ear.     

Potential anti-tumor promoting activity of lupane-type triterpenoids from the stem bark of Glochidion zeylanicum and Phyllanthus flexuosus

Four known lupane-type triterpenoids, glochidonol (1), glochidiol (2), lup-20(29)-ene-1beta,3beta-diol (3) and glochidone (3) were isolated from the stem bark of Glochidion zeylanicum. Previously, lupeol (5), lup-20(29)-ene-3beta,24-diol (6) and betulin (7) were isolated from the stem bark of Phyllanthus flexuosus. This study reports the assays of these lupane-type triterpenoids: all isolates 1-7 and synthetic analogues, glochidonyl acetate (1a), lup-20(29)-ene-1,3-dione (1b) and lup-20(29)-ene 3beta,24-diacetate (6a) were tested for their inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol 13-acetate (TPA). Among them, the effects of compounds 2 (IC50 = 290 mol ratio/32 pmol TPA) and 3 (IC50 = 300) were stronger than the others. In addition, compound 2 exhibited a strong inhibitory effect on mouse skin tumor promotion in an in vivo mouse two-stage carcinogenesis test.     

QT PRODACT: evaluation of the potential of compounds to cause QT interval prolongation by action potential assays using guinea-pig papillary muscles

Certain compounds that prolong QT interval in humans have little or no effect on action-potential (AP) duration used traditionally, but they inhibit rapidly-activated-delayed-rectifier potassium currents (IKr) and/or human ether-a-go-go-related gene (hERG) currents. In this study using isolated guinea-pig papillary muscles, we investigated whether new parameters in AP assays can detect the inhibitory effects of various compounds on IKr and/or hERG currents with high sensitivity. The difference in AP duration between 60% and 30% repolarization, 90% and 60% repolarization, and 90% and 30% repolarization (APD30-60, APD60-90, and APD30-90, respectively) were calculated as the new parameters. All the 15 IKr and/or hERG current inhibitors that have been reported (9 compounds) or not reported (6 compounds) to inhibit calcium currents prolonged APD30-60, APD60-90, and/or APD30-90; and 8 of the 15 inhibitors prolonged APD30-60, APD60-90, and/or APD30-90 more potently than APD90. The APD30-60, APD60-90, and APD30-90 measurements revealed no difference in sensitivity when evaluating the effects of the IKr and/or hERG current inhibitors on the three parameters. On the other hand, compounds with little or no effect on hERG currents had no effect on APD30-60, APD60-90, or APD30-90. Therefore, it is concluded that in AP assays using isolated guinea-pig papillary muscles, APD30-60, APD60-90, and APD30-90 are useful indexes for evaluating the inhibitory effects of compounds including mixed ion-channel blockers on IKr and/or hERG currents.     

ABC transporters of pathogenic fungi: recent advances in functional analyses]

ABC (ATP binding cassette) transporters consist of transmembrane domains which confer specificity, and structurally conserved nucleotide binding domains that contain highly conserved amino acid motifs. They act not only as transporters but also as receptors or channels that use energy generated by ATP hydrolysis. ABC transporters are widely dispersed in nature. They are found in cells ranging from prokaryotes (bacteria) to eukaryotes (including humans) and several are considered to play crucial roles in cellular homeostasis. Defects in ABC transporters in humans are associated with severe diseases such as type 2 diabetes and cystic fibrosis. Some ABC transporters extrude xenobiotics and confer resistance to chemotherapeutics on microbial pathogens and cancer cells. Thus ABC transporters are of considerable medical importance. Structure-function analysis of ABC transporters has begun to elucidate their mechanisms of substrate recognition, the functional regulation of ATP-binding and hydrolysis and to identify intrinsic physiological functions. In pathogenic fungi, ABC transporters contribute to the clinical problem of drug resistance. The application of new technologies to the examination of fungal ABC transporter function is providing new insights into the use of antifungal drugs in medical mycology and contributing to a better understanding of these important membrane proteins.     

Lag-phase autophagy in the methylotrophic yeast Pichia pastoris

When microbes sense environmental changes, they often temporarily attenuate cell growth to adapt to the new situations, showing a lag phase. In this study, we report that the methylotrophic yeast, Pichia pastoris , induced autophagy during the lag phase after the cells were shifted from glucose to methanol medium. Through the autophagic process at least two proteins, aminopeptidase I precursor and cytosolic aldehyde dehydrogenase, were found to be transported into the vacuole, which was dependent on PpAtg11 and PpAtg17, respectively. Notably, PpAtg1 and PpAtg17 were required for early exit from the lag phase during the methanol adaptation. In accordance, phosphorylation states of elongation initiation factor 2α indicated reductions of intracellular amino-acid pools in the atg mutant strains. Together, these data demonstrate the importance of amino acid recycling by autophagy during a cell-remodeling process.     

The prevention of iatrogenic spinal cord injury utilizing the evoked spinal cord potential

Summary The evoked spinal cord potential elicited by direct stimulation of the cord has been used clinically to monitor cord function in the course of operations on the spine. The technique used allows measurement of a relatively large amplitude of potential, which is fairly stable against anaesthetics and related drugs, by means of a simple recording system and is sensitive enough to indicate cord damage. Continuous monitoring can easily be carried out. We have encountered no complications when using this method on 99 patients.

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Résumé Le potentiel évoqué provoqué par la stimulation directe de la moelle épinière a été utilisé en clinique pour contrôler la fonction de la moelle lors des interventions sur le rachis. Cette technique permet de mesurer une assez grande amplitude de potentiel, qui est relativement stable à l'égard des anesthésiques et d'autres drogues de même type, grâce à un système simple d'enregistrement; il est suffisamment sensible pour détecter des altérations de la moelle. Une surveillance continue peut aisément être effectuée. Aucun incident n'a été rencontré chez 99 malades lors de l'utilisation de cette méthode.

     

Comparison of remnant-like lipoprotein particles in postmenopausal women with and without coronary artery disease and in men with coronary artery disease

It is known that hypertriglyceridemia is a risk factor of coronary artery disease (CAD) in postmenopausal women. This study prospectively examined whether remnant lipoprotein, an atherogenic triglyceride-rich lipoprotein, may have a significant risk and prognostic values in postmenopausal women with angiographically verified CAD. Remnant-like lipoprotein particles cholesterol (RLP cholesterol) levels in fasting serum were measured in 134 consecutive postmenopausal women with (n = 56) or without (n = 78) CAD by an immunoseparation method. The women with CAD were followed for ≤24 months until occurrence of the following clinical coronary events: readmission or coronary revascularization due to recurrent or refractory angina pectoris, nonfatal myocardial infarction, and cardiac death. Multivariate logistic regression analysis showed that high RLP cholesterol levels (>5.7 mg/dl cholesterol; 90th percentile of the distribution of RLP cholesterol levels in controls) were a significant risk factor for the presence of CAD independent of low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, and other traditional risk factors. Kaplan-Meier analysis demonstrated that women with CAD and higher RLP cholesterol levels had a significantly higher probability of developing coronary events (p <0.001). In multivariate Cox hazard analysis, high RLP cholesterol levels as well as diabetes and hypercholesterolemia were a significant predictor of future coronary events independent of other risk factors in women with CAD (odds ratio 9.7, 95% confidence intervals 1.3 to 20.3, P = 0.02). In conclusion, increased levels of RLP cholesterol are a significant and independent risk factor of CAD and predict future coronary events in postmenopausal women with CAD.