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Biomedical subjects

A Ernst

Publications and source records attributed to A Ernst.

At least 19 recordsLinked to original sources

Intraoperative monitoring by transtympanic electrocochleography and brainstem electrical response audiometry in acoustic neuroma surgery.

The preservation of hearing is a major aim of contemporary temporal bone surgery. Our present findings demonstrate that intraoperative monitoring is a key method for attaining serviceable postoperative hearing after the removal of an acoustic neuroma. Both electrocochleography (ECoG) and brainstem electrical response audiometry were performed in 96 patients operated on for acoustic neuromas. The specificity of the different monitoring methods was affected by surgical manipulations in addition to such non-specific influences as CSF drainage, core body temperature and anesthesia. In the present study ECoG was found to be more reliable in assessing the intra- and postoperative course with respect to the preservation of cochlear function.

Audiometry, Evoked Response

Electrophysiological responses of the cochlea to transient asphyxia are influenced by arachidonate metabolites.

The influence of a transient asphyxia on cochlear potentials, i.e. endolymphatic potential (EP), summating potential (SP) and cochlear microphonics (CM) was investigated in guinea pigs when pretreating the animals with various substances interacting with the arachidonic acid (AA) cascade at the level of thromboxane. The controls showed the well-known decline of the EP, CM and the SP increase. When infusing a thromboxane synthetase inhibitor (dazoxiben) or two different thromboxane receptor blockers (daltroban or sulotraban) before the 3-minutes' period of asphyxia was started, the electrophysiological responses of the inner ear (cochlea) could significantly be influenced. The results indicate that a shift of the thromboxane (TXA2)/prostacyclin (PGI2)-balance in favour of the last improve the metabolic conditions for a survival of the cochlea when it is challenged.

Analysis of Variance

Stiffness, compliance, elasticity and force generation of outer hair cells.

Isolated outer hair cells (OHCs) were partially sucked into especially designed cell capillaries allowing an experimental reconstitution of the cells' electroanatomy. The experimental approach separated the apical from the basolateral parts of the cells thus forming an artificial scala media and scala tympani. Resistance between both was 121 +/- 42 M omega. A sequence of negative and positive pressures was applied to the basal cell pole allowing "pulling" or "pushing" of the sensory cell investigated. The resulting length changes together with the known pressures allowed the estimation of an actual longitudinal compliance of 354 +/- 35 m/N. Following "pulling" OHCs tended to resume their initial shape after the force had ceased to be effective indicating elastic distortions. The calculated elasticity modulus of OHCs amounted to 6.1 +/- 3.4 kN/m2. From this data an actual longitudinal whole cell stiffness of OHCs of 3 x 10(-3) N/m was calculated. Ultrasound scanning of immobilized OHCs identified the cuticular plate (CP) and a central core between CP and basal cell pole as structures contributing to the cells' acoustic stiffness. Changes of the potential differences between the artificial scala media and scala tympani resulted in active length changes following the command voltage with a slope of delta 1/(1 x U) = 0.055 V-1. Assuming the validity of Hooke's law, the force generation associated with the active length changes can be calculated since the compliance is known.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Myocardial contrast echocardiography: influence of ischaemia and hyperaemia in an animal model.

To evaluate changes in myocardial contrast echocardiography during ischaemia and hyperaemia, contrast studies were performed in 16 open chest dogs. Time-intensity curves were generated using videodensitometry after contrast injections to demonstrate ischaemic and non-ischaemic areas of interest during a wide range of coronary blood flow levels. For each time-intensity curve, the peak contrast intensity (PCI), washout halftime (T1/2) and area under the curve (AUC) were calculated. PCI and AUC decreased significantly only with severe ischaemia (90% or more reduction in flow), and increased significantly with hyperaemia of more than 2.5 times baseline flow. Both ischaemia and hyperaemia were found to prolong the T1/2. There was only a moderate linear correlation between the magnitude of hyperaemia and myocardial contrast echocardiographic parameters. There was significantly less increase in myocardial contrast echocardiographic parameters during hyperaemia in segments supplied by a stenosed coronary artery.

Albumins

Synthesis of nitrogenase in mutants of the cyanobacterium Anabaena sp. strain PCC 7120 affected in heterocyst development or metabolism.

Mutants of Anabaena sp. strain PCC 7120 that are incapable of sustained growth with air as the sole source of nitrogen were generated by using Tn5-derived transposons. Nitrogenase was expressed only in mutants that showed obvious morphological signs of heterocyst differentiation. Even under rigorously anaerobic conditions, nitrogenase was not synthesized in filaments that were unable to develop heterocysts. These results suggest that competence to synthesize nitrogenase requires a process that leads to an early stage of visible heterocyst development and are consistent with the idea that synthesis of nitrogenase is under developmental control (J. Elhai and C. P. Wolk, EMBO J. 9:3379-3388, 1990). We isolated mutants in which differentiation was arrested at an intermediate stage of heterocyst formation, suggesting that differentiation proceeds in stages; those mutants, as well as mutants with aberrant heterocyst envelopes and a mutant with defective respiration, expressed active nitrogenase under anaerobic conditions only. These results support the idea that the heterocyst envelope and heterocyst respiration are required for protection of nitrogenase from inactivation by oxygen. In the presence of air, such mutants contained less nitrogenase than under anaerobic conditions, and the Fe-protein was present in a posttranslationally modified inactive form. We conclude that internal partial oxygen pressure sufficient to inactivate nitrogenase is insufficient to repress synthesis of the enzyme completely. Among mutants with an apparently intact heterocyst envelope and normal respiration, three had virtually undetectable levels of dinitrogenase reductase under all conditions employed. However, three others expressed oxygen-sensitive nitrogenase activity, suggesting that respiration and barrier to diffusion of gases may not suffice for oxygen protection of nitrogenase in these mutants; two of these mutants reduced acetylene to ethylene and ethane.

Anabaena

In vitro activation of dinitrogenase reductase from the cyanobacterium Anabaena variabilis (ATCC 29413).

Nitrogenase of the heterocystous cyanobacterium Anabaena variabilis was inactivated in vivo (S. Reich, H. Almon, and P. Böger, FEMS Microbiol. Lett. 34:53-56, 1986). Partially purified and modified (inactivated) dinitrogenase reductase (Fe-protein) of such cells was reactivated by isolated membrane fractions of A. variabilis or of Rhodospirillum rubrum, and acetylene reduction was measured. Reactivation requires ATP, Mg2+, and Mn2+. The activating principle is localized in the heterocyst and was found effective only when prepared from cells exhibiting active nitrogenase. It also restores the activity of modified Fe-protein from R. rubrum.

Acetylene

[Clinical applications and importance of selected, modern results of hearing research].

Inner ear physiology has largely contributed to clinical progress in otolaryngology within the last decade. The cell biological knowledge of basic properties of outer hair cells and their motility in particular helped to explain the unique sharp frequency dispersion in the cochlea and other mechanisms of hearing. Further important aspects with a clinical impact have been e.g. the description of the cellular mechanism in aminoglycoside ototoxicity, a pathophysiological concept of Ménière's disease and the application of otoacoustic emissions in audiological testing of infants.

Aminoglycosides

Ability of high-intensity ultrasound to ablate human atherosclerotic plaques and minimize debris size.

To investigate whether high-intensity ultrasound can destroy atherosclerotic plaques while sparing the normal arterial wall, 279 normal human aortic sites and 119 fibrous and 193 calcified plaques, obtained from 24 necropsies, were insonified in a water tank, at 20 kHz and at 5 different power intensities, ranging from 68 W/cm2 (P1) to 150 W/cm2 (P5). These intensities were associated with a total excursion of the ultrasound irradiation apparatus tip from 90 to 268 microns, respectively. Time to perforate normal aortic sites and fibrous and calcified plaques was recorded at each intensity. There was no difference in perforation time between normal aortic sites and fibrous and calcified plaques when high-power levels (P2 to P5) were used. However, at the lowest power (P1), perforation time for the normal aortic wall was significantly longer than for fibrous and calcified plaques: 30 +/- 18 seconds (166 observations), 14 +/- 7 seconds (p less than 0.001) (78 observations) and 12 +/- 8 seconds (p less than 0.001) (115 observations), respectively. When perforation times for normal vessel wall versus fibrous plaque and normal vessel wall versus calcified plaque from the same necropsy specimen were compared in a pairwise manner, the results were: 29 +/- 13 vs 16 +/- 7 (p less than 0.001) (48 paired observations) and 26 +/- 9 vs 10 +/- 5 seconds (p less than 0.001) (55 paired observations), respectively. Regardless of whether paired or unpaired comparison was applied, no significant difference was found in perforation time between fibrous and calcified plaques. The debris did not differ in size as measured separately for normal sites and fibrous and calcified plaques by a computer-interfaced Channelizer and Coulter Counter system.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Stat RPRs.

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Emergencies

PAF receptor antagonists influence asphyxia-induced changes of the inner ear.

The influence of a transient asphyxia on cochlear potentials, i.e. endolymphatic potential (EP), summating potential (SP) and cochlear microphonics (CM) was investigated in guinea pigs which were injected with two different PAF receptor antagonists before. It could be shown that apafant (WEB 2086) and bepafant (WEB 2170) significantly reduced the asphyxia-induced potential changes compared to controls. The results suggest a mediating role of PAF in the asphyxia model. The impact of the findings for therapeutics is discussed.

Animals

Increased serum sulfate concentrations in man due to environmental factors: effects on acetaminophen metabolism.

Serum sulfate concentrations were determined in volunteers consuming municipal drinking water with varying sulfate contents--77 ppm in Saskatoon and 1157 ppm in Rosetown. The serum sulfate concentrations were subsequently monitored after the administration of single or multiple-dosing regimens of acetaminophen, which undergoes sulfoconjugation, to determine whether sulfate concentrations in serum changed. Average serum sulfate concentrations were 0.35 mmol/L (Saskatoon) and 0.50 mmol/L (Rosetown). Saskatoon volunteers had a significant fall in serum sulfate concentrations during the multiple-dosing regimen. This was not seen in the Rosetown participants. The rates of urinary excretion and renal clearance of sulfate were significantly higher in the Rosetown volunteers. Except for the multiple-dosing t1/2 levels, the Cmax, tmax, AUC and Cl/f of acetaminophen were not significantly different within or between the 2 groups. The excretion of sulfate and glucuronide conjugates of acetaminophen was not significantly different between the 2 groups, but there was a difference within each group with respect to single and multiple-doses. Excretion of the sulfate conjugate fell significantly in the Saskatoon volunteers during the multiple-dose portion of the study, whereas the percentage excreted as the glucuronide increased. The consumption of 15-fold greater sulfate levels in drinking water increased the sulfate concentration in serum. However, this increased concentration did not significantly alter the sulfoconjugation of acetaminophen.

Acetaminophen

Non-invasive detection of reduced regional myocardial perfusion at rest in patients with unstable angina pectoris: increased regional 81mKr deposition following intravenous injection of 81Rb.

The present study was to investigate whether combined imaging of 81Rb and 81mKr distributions after i.v. injection of 81Rb at rest might improve the differentiation between ischemic and irreversibly damaged myocardium as compared to 201Tl scintigraphy at rest. In 21 patients who had undergone diagnostic cardiac catheterization for evaluation of chest pain, 148 MBq ultrapure 81Rb were injected i.v. at rest immediately following 201Tl scintigraphy at rest. Of 14 patients with earlier myocardial infarction, 10 patients revealed decreased regional tracer uptake of 81Rb and/or 81mKr, compared to 12 patients with regional 201Tl uptake abnormalities. In 3 patients with unstable angina pectoris, however, an evident mismatch between either the regional 201Tl or 81Rb distributions and the distribution of 81mKr was observed: in contrast to the reduced uptake of 201Tl and/or 81Rb, 81mKr activity was increased in 3 myocardial segments with normal left ventricular performance but supplied by coronary arteries with high-grade stenoses. In patients with contraindications to exercise tests (e.g. unstable angina) 81Rb/81mKr rest scintigraphy may therefore assist the differentiation between malperfused but potentially viable and irreversibly damaged myocardium.

Angina, Unstable

Bypass of a primase requirement for bacteriophage T4 DNA replication in vivo by a recombination enzyme, endonuclease VII.

A primase, the product of phage T4 gene 61, is required to initiate synthesis of Okazaki pieces and to allow bidirectional replication from several T4 origins. However, primase-defective T4 gene 61 mutants are viable. In these mutants, leading-strand DNA synthesis starts at the same time as in wild type infections, but, in contrast to wild type, initiation is unidirectional and the first replicative intermediates are large displacement loops. Rapid double-strand DNA replication occurs later after infection, generating multiple branched concatemers, which are cut and packaged into viable progeny particles, as in wild-type T4. Evidence is presented that this late double-strand DNA replication requires functional endonuclease VII (endo VII), the product of the T4 gene 49. We propose that endo VII can provide a backup mechanism when primase is defective, because it cuts recombinational junctions, generating 3' ends. These ends can prime DNA synthesis to copy the DNA strands that had been displaced during the initial origin-dependent replication. We explain the DNA-delay phenotype and the commonly observed temperature dependence of DNA replication in primase-deficient gene 61 mutants as a consequence of temperature-dependent translational control of gene 49 expression. In the presence or absence of functional primase endo VII is essential for correct packaging of DNA. The powerful selection that keeps the function of endo VII and expression of its gene at levels that are optimal for T4 development determines both the efficiency and the limitations of the bypass mechanism.

Base Sequence

Modification of dinitrogenase reductase in the cyanobacterium Anabaena variabilis due to C starvation and ammonia.

In the heterocystous cyanobacterium Anabaena variabilis, a change in nitrogenase activity and concomitant modification of dinitrogenase reductase (the Fe protein of nitrogenase) was induced either by NH4Cl at pH 10 (S. Reich and P. Böger, FEMS Microbiol. Lett. 58:81-86, 1989) or by cessation of C supply resulting from darkness, CO2 limitation, or inhibition of photosystem II activity. Modification induced by both C limitation and NH4Cl was efficiently prevented by anaerobic conditions. Under air, endogenously stored glycogen and added fructose protected against modification triggered by C limitation but not by NH4Cl. With stored glycogen present, dark modification took place after inhibition of respiration by KCN. Reactivation of inactivated nitrogenase and concomitant demodification of dinitrogenase reductase occurred after restoration of diazotrophic growth conditions. In previously C-limited cultures, reactivation was also observed in the dark after addition of fructose (heterotrophic growth) and under anaerobiosis upon reillumination in the presence of a photosynthesis inhibitor. The results indicate that modification of dinitrogenase reductase develops as a result of decreased carbohydrate-supported reductant supply of the heterocysts caused by C limitation or by increased diversion of carbohydrates towards ammonia assimilation. Apparently, a product of N assimilation such as glutamine is not necessary for modification. The increase of oxygen concentration in the heterocysts is a plausible consequence of all treatments causing Fe protein modification.

Aerobiosis

Statistics of the physiologic phase of integrated backscatter from canine myocardium with normal and reduced coronary circulation.

The phase, relative to the arterial pressure, of cyclically varying integrated backscatter from canine myocardium was measured at normal and reduced coronary blood flow levels and was found to become more randomized with decreasing flow. The phase, modeled as a von Mises distribution on a unit circle which is very similar to the normal distribution on the line, is characterized by a mean (mu 0) and a concentration or width parameter (kappa). kappa is used to characterize the degree of randomization. The von Mises distribution provides an excellent fit to measured data (p less than 0.01). Hypothesis tests performed on the data for various coronary flow levels indicate that the phase distribution for normal coronary flow level is significantly different from the distributions at other flow levels (p less than 0.05). The results suggest that the parameter kappa may be used for differentiating normal and ischemic myocardium.

Animals

Arachidonate metabolites change furosemide-induced cochlear potentials.

Furosemide-induced changes of cochlear potentials were used as a model to study the influence of arachidonic acid metabolites on ion movements within the cochlea. No influence was exerted by the drugs Esculetin - blocking the synthesis of lipoxygenase products - and Dazoxiben - suppressing thromboxane A2 levels within the cochlea. A weakening of the furosemide-induced changes of the endocochlear potential was found when infusing the thromboxane (TX) receptor antagonists BM 13,505 and BM 13,177 before furosemide was given. This effect was also observed when pre-treating the guinea pig with a specific platelet-activating factor receptor antagonist, BN 52,021, before the diuretics was given. Summating potential and cochlear microphonics remained insignificantly changed against controls. The results suggest that a TX receptor contributes to the control of ion movements within the cochlea. A possible involvement of loop diuretics' receptors is discussed.

Acoustic Stimulation

The effect of PAF in the cochlea of guinea pigs.

The influence of 10(-10) and 10(-9) M PAF/animal given into the jugular vein over 30 sec on inner ear potentials, i.e. endolymphatic potential (EP), summating potential (SP) and cochlear microphonics (CM) was investigated. The EP showed the most pronounced changes. When infusing a specific PAF receptor antagonist, ginkgolide B, or the TXA2 receptor antagonist, sulotraban, before the the infusion of PAF, the changes in cochlear potentials could be completely prevented. A second TXA2 receptor antagonist, daltroban, did not effectively prevent PAF actions. It is hypothesized that these PAF effects are due to an interference with ion transport in the non-sensory structures of the inner ear.

Acoustic Stimulation

The time-course of furosemide-induced strial changes in guinea pigs after pretreatment with daltroban.

It was shown previously (Ernst et al., 1989) that pretreatment of guinea pigs with a thromboxane (TX) receptor antagonist attenuates the decline of the endocochlear potential (EP) induced by furosemide. The present paper is aimed at investigating a possible correlation between the electrophysiological data and ultrastructural changes of the stria vascularis by electron microscopy. The dosages of 40, 60, and 80 mg/kg furosemide were injected after the pretreatment with the TX receptor antagonist daltroban and compared to controls which were injected with furosemide only. It was found at all furosemide concentrations that the strial changes 10 min after injection were nearly unchanged against controls. 30 min after furosemide injection, the most pronounced changes were seen when pretreating the animals: a clear reduction of the marginal cell swelling and edema in general were observed at 40 and 60 mg/kg furosemide. The guinea pigs injected with 80 mg/kg furosemide after pretreatment displayed nearly the same changes as controls.

Animals