The generation of DC potentials in a computational model of the organ of Corti: effects of voltage-dependent K+ channels in the basolateral membrane of the inner hair cell

A computational model of the organ of Corti is described to assist in the interpretation of electrophysiological data concerning the role of the K+ channels residing in the basolateral membrane of cochlear hair cells. Recent in vivo data from Van Emst et al. (Hear. Res. 88, 27-35 (1995); Hear. Res. 102, 70-80 (1996)) about the effects of selective blocking of K+ channels indicate that these channels affect the magnitude of the summating potential. In order to understand the nature of this effect, the model of Dallos (Hear. Res. 14, 281-291 (1984)) was extended to account for the voltage- and time-dependent properties of the K+ channels in the basolateral membrane of the inner hair cell (IHC) (Kros and Crawford, J. Physiol. 421, 262-291 (1990)). The model shows that the K+ channels induce a shift in the mean IHC basolateral conductance when high-frequency stimuli are present. As a result, cochlear transduction shifts to a different electrical operating state and this is the source of a marked decrease in the stimulus-evoked DC response of the IHC. Extracellularly, in contrast, the magnitude of the DC response increases slightly. At low frequencies, the K+ channels respond to the stimulus waveform on a cycle-by-cycle basis. The waveform distortion associated with this dynamic basolateral impedance induces a further decrease in the intracellular stimulus-evoked DC response of the IHC. Thus, K+ channels in the IHC appear to be directly involved in the generation of the DC receptor potential at low frequencies, but at high frequencies they simply modify the size of the DC response.     

Chronic administration of dexamethasone results in Fc receptor up-regulation and inhibition of class I antigen expression on macrophages from MRL/lpr autoimmune mice

OBJECTIVE: To assess the influence of hypertensive disorders in pregnancy on the subsequent risk of placental abruption and uterine bleeding of unknown aetiology, and to examine the combined effects of hypertensive disorders and cigarette smoking during pregnancy on the risk of uteroplacental bleeding disorders. DESIGN: Retrospective cohort study. SETTING: Data for this study were derived from the Nova Scotia Atlee Perinatal database, Canada, comprising of women who were delivered in the province between 1980 and 1993. POPULATION: 120,666 pregnancies resulting in singleton births, of which 13,360 pregnancies were complicated by pre-eclampsia and/or chronic hypertension. MAIN OUTCOME MEASURES: Risks and relative risks of placental abruption and uterine bleeding of unknown aetiology in pregnancies complicated by chronic hypertension, mild and severe pre-eclampsia, and chronic hypertension with superimposed pre-eclampsia, each compared with normotensive patients. Adjusted relative risks were obtained through the fit of multivariable logistic regression models based on the method of generalised estimating equations. RESULTS: Chronically hypertensive women had no increased risk of abruption (RR 1.4; 95% CI 0.5-3.6), while women whose pregnancies were complicated by severe pre-eclampsia (RR 3.8; 95% CI 2.1-6.9), and chronic hypertension with superimposed pre-eclampsia (RR 2.8; 95% CI 1.2-6.3) showed strong associations with placental abruption. However, none of the hypertensive disorders were associated with uterine bleeding of unknown aetiology. The association between placental abruption and hypertensive disorders varied by parity. Parous women with chronic hypertension and superimposed pre-eclampsia were at greater risk of placental abruption (aRR 3.8; 95% CI 1.9-7.8) than nulliparous women with chronic hypertension and superimposed pre-eclampsia (aRR 1.6; 95% CI 0.5-4.9). The joint effects of smoking and hypertension had a greater effect on the risk of placental abruption than would have been expected based on their individual effects. CONCLUSIONS: The pattern of association between placental abruption and hypertension varied in relation to the specific type of hypertensive disorder. However, uterine bleeding of unknown aetiology was not associated with hypertension. Findings from this study suggest that placental abruption and uterine bleeding of unknown origin are aetiologically distinct obstetric complications with respect to hypertensive disorders during pregnancy.     

Direction of the clinical pathomorphosis of alcoholic delirium

An examination of 348 patients with alcoholic delirium permitted to detect the main directions in the evolutional variability of the clinical picture. The authors distinguished 3 types in the development of a delirium: short-term with a complete and incomplete (abortive) variant; typical delirium with mono-and polymorphic structure of the syndrome; a protracted development in the form of a severe psychoses of a complex structure and a sluggish protracted variant with an obliviated symptomatology.     

The nature of diseases: evolutionary, thermodynamic and historical aspects

Physico-chemical sciences are dominated by the deterministic interpretation. Scientific medicine has generally been assigned to the area of functional biology and thence to the physico-chemical sciences. In as much as diseases are alterations of physiological processes, they share the ontological status of the latter. However, many diseases cannot be accommodated within a deterministic interpretation. First, many diseases are initiated by errors in transmission of information and followed by natural selection. These diseases, such as tumoural transformations and autoimmune processes, behave as evolutionary processes. Second, physiological processes do not cause irreversible changes while diseases may do so when not followed by restitutio ad integrum. The tendency of living organisms to maintain stationary states of great stability and minimum energy dissipation is largely due to intermolecular forces-stabilized structures, the information for which is selected during phylogenesis and decodified during ontogenesis. Diseases cause alterations of the biological structures, thereby shifting living organisms toward stationary states of lower stability and increased dissipation. The shift, reversible or irreversible, to less stable and efficient stationary states is a common thermodynamic feature of diseases. In spite of the uniqueness of their genotype, living organisms, during ontogenetic development, form spatio-temporal unrestricted classes of infinite membership. Neither stationarity nor environment-induced perturbations and consequent adaptations are sources of historicity because of the genomic programme constraint. Historicity is conferred, however, to each organism by the permanent record of such unique events as: a) the variation-selection processes occurring in the brain-mind and immunological systems; and b) irreversible alterations induced by diseases. The disease-induced changes have ontological and epistemological consequences. Since biological structures and functions are transformed into individual, historical entities, the laws of scientific medicine must be applied in clinical practice to higher levels of organization, namely to the ensembles or groups of individuals affected by the diseases.