Effects of noise on cochlear potentials and endolymph potassium concentration recorded with potassium-selective electrodes

Guinea pig cochleas were exposed to either broad-band noise at intensities between 95 and 115 dBA or octave-band noise centered at 380 Hz or 4.2 kHz at intensities between 115 and 125 dB SPL. Cochlear microphonics (CM), summating potentials (SP) and action potentials (AP) were recorded from differential electrodes in the perilymphatic scalae between successive 20-min periods of noise exposure. The endocochlear potential (EP) and endolymph potassium concentration [Kendo+] were recorded continuously from scala media using double-barreled potassium-sensitive electrodes. It was found that the initial exposure to noise at 115 dBA produced considerable suppression of the CM and AP, while the EP and [Kendo+] were elevated above their normal values. When animals previously treated with kanamycin were subjected to the same level of noise exposure no systematic increase in either EP ro [Kendo+] was observed. After prolonged exposure to 380 Hz octave-band noise at 125 dB SPL, a slow decline of EP and [Kendo+] was observed. The relationships between the changes in EP, [Kendo+] and CM are discussed.     

Prevention of recurrence and prolonged survival in primary central nervous system lymphoma (PCNSL) patients treated with adjuvant high-dose methylprednisolone

Five patients at risk for primary central nervous system lymphoma (PCNSL) recurrence were treated with high-dose methylprednisolone (HDMP) to prevent 'trafficking' of malignant lymphocytes into the central nervous system (CNS). HDMP was chosen because of its ability to stabilize the 'blood brain barrier (BBB)'. Three men with newly diagnosed PCNSL, ages 62, 76 and 78y, whose survival was projected to be 6.6 months, began treatment after achieving complete response (CR) to initial radiation therapy alone and survived 27, 37 and 59 months after treatment. In none was death from recurrent disease in CNS but one patient did die of systemic non-Hodgkin's lymphoma (NHL) five years after PCNSL diagnosis. A 20 y old man was treated with HDMP after successful combined modality therapy and is alive 75+ months after initial diagnosis without evidence of disease recurrence. A 34 y old man relapsed after combined modality initial treatment and failed to respond to HDMP when treatment was begun after unsuccessful salvage therapy; he died of disease 12 months after initial diagnosis. There were no treatment complications. The promising results in this pilot study from the basis for a North Central Cancer Treatment Group (NCCTG) 96-73-51, a Phase 2 clinical trial of brain radiotherapy and HDMP for PCNSL patients 70y of age and older, a group of patients at high risk for toxicity from intensive combined modality therapy.     

Calcium gradients in inner ear endolymph

Recent studies suggest that endolymphatic hydrops resulting from the ablation of the endolymphatic duct and sac in guinea pigs may be caused by a disturbance of endolymph calcium homeostasis. A similar disturbance of calcium homeostasis could represent the underlying cause of Ménière's disease. In this study, we mapped the calcium concentrations and electrical potentials throughout the endolymphatic system in normal guinea pigs. Large concentration differences exist between different compartments, including a more than twofold increase along the length of the cochlea. The electrochemical potential for calcium (the force driving passive longitudinal calcium movement) was calculated for all the endolymphatic compartments. The results show that endolymph is extremely inhomogenous with respect to calcium potentials. On the basis of these potentials, it appears that calcium is transported into endolymph in the cochlea and out of endolymph in the saccule and utricle. The possibility that endolymphatic hydrops arises from a disturbance in longitudinal flow of calcium, rather than in longitudinal volume flow, is considered.     

Lymphangiomas in children: MR imaging

Seventeen lymphangiomas in 15 patients were imaged with magnetic resonance (MR) to define the nature, extent, and anatomic relationships of these lesions. The MR and pathologic findings were then compared to determine the histologic basis for the signal-intensity characteristics of these lesions. The signal intensity of 13 lesions was similar to or slightly less than that of muscle on T1-weighted images and greater than that of fat on T2-weighted images. This appearance correlated with the presence of ectatic lymphatic channels containing clear fluid on histologic section. Four lymphangiomas had high signal intensity, approximately equal to that of fat, on T1-weighted images, reflecting the presence of clotted blood or small cystic spaces with a higher ratio of fat to fluid. Sixteen of 17 lesions had visible septations on MR images. The authors' experience suggests that most lymphangiomas have a characteristic appearance on MR images. The information obtained with MR imaging can help in providing a preoperative diagnosis, in planning surgical resection, and in defining recurrence.     

Modulatory effects of serotonin on excitatory amino acid responses and sensory synaptic transmission in the ventrobasal thalamus

Excitatory amino acid receptors are thought to mediate sensory input to the ventrobasal thalamus. There is evidence for a brainstem serotonergic projection to the ventrobasal thalamus which may have a modulatory role. The possibility that serotonin may selectively modulate responses to excitatory amino acid receptor agonists, and its effects on sensory synaptic transmission has been examined in the rat ventrobasal thalamus in vivo. Iontophoretic ejection of serotonin at low currents produced a marked facilitation of responses to excitatory amino acids. In contrast, excitatory responses to cholinomimetic agonists were attenuated. Synaptic transmission was concomitantly enhanced or unchanged in these circumstances. Higher serotonin ejection currents reversed the facilitation, or inhibited excitatory amino acid responses and synaptic transmission. It is concluded that serotonin can modulate responses to excitatory amino acids relatively selectively and that synaptic transmission of somatosensory information through the ventrobasal thalamus may be susceptible to brainstem serotonergic modulation.     

Endotoxin protection against oxygen toxicity and its reversal by acetylsalicylic acid

This study investigated the involvement of substances derived from arachidonic acid in the mechanism of endotoxin's protective action against pulmonary oxygen toxicity. Eighty-three percent of rats treated with a small dose of endotoxin (1 mg/kg) survived exposure to over 95% oxygen for 7 days. In contrast, all control rats exposed to the same oxygen concentration died within 3 days. When the endotoxin-treated rats were also treated with the soluble lysine salt of acetylsalicylic acid (100 mg/kg), 7-day survival decreased to 25%. This suggests that prostaglandin metabolism may play an important role in the protective action of endotoxin during hyperoxia.     

Deep venous thrombosis of the leg: US findings

In a prospective study, 121 consecutive patients with a clinical diagnosis of deep venous thrombosis of the leg were examined with real-time ultrasonography. The findings were correlated with the results of venography. The common femoral vein and the popliteal vein were evaluated for intraluminal echoes and compressibility, and the common femoral vein was also evaluated for an increase in diameter in response to the Valsalva maneuver. The superficial femoral vein and the calf veins were not evaluated. The results indicate that compressibility of the common femoral and popliteal veins is the best indication of deep venous thrombosis, with a sensitivity of 96% and a specificity of 97%. The accuracy of detection was not improved by including data from thrombus visualization or the response of the common femoral vein to the Valsalva maneuver.     

Quantification of solute entry into cochlear perilymph through the round window membrane.

The administration of drugs to the inner ear via the round window membrane is becoming more widely used for both clinical and experimental purposes. The actual drug levels achieved in different regions of the inner ear by this method have not been established. The present study has made use of simulations of solute movements in the cochlear fluids to describe the distribution of a marker solute in the guinea pig cochlear fluid spaces. Simulation parameters were derived from experimental measurements using a marker ion, trimethylphenylammonium (TMPA). The distribution of this ion in the cochlea was monitored without volume disturbance using TMPA-selective microelectrodes sealed into the first and second turns of scala tympani (ST). TMPA was applied to perilymph by irrigation of the intact round window membrane with 2 mM solution. At the end of a 90 min application period, TMPA in the first turn, 1.4 mm from the base of ST, reached an average concentration of 330 microM (standard deviation (S.D.) 147 microM, n = 8). TMPA in the second turn, 7.5 mm from the base of ST reached a concentration of 15 microM (S.D. 33 microM, n = 5). The measured time courses of TMPA concentration change were interpreted using the Washington University Cochlear Fluids Simulator (V 1.4), a public-domain program available on the internet at http ://oto.wustl.edu/cochlea/. Simulations with parameters producing concentration time courses comparable to those measured were: (1) round window permeability: 1.9 x 10(-80 cm/s; (2) ST clearance half-time: 60 min; (3) longitudinal perilymph flow rate: 4.4 nl/min, directed from base to apex. Solute concentrations in apical regions of the cochlea were found to be determined primarily by the rate at which the solute diffuses, balanced by the rate of clearance of the solute from perilymph. Longitudinal perilymph flow was not an important factor in solute distribution unless the bony otic capsule was perforated, which rapidly caused substantial changes to solute distribution. This study demonstrates the basic processes by which substances are distributed in the cochlea and provides a foundation to understand how other applied substances will be distributed in the ear.     

Cytotoxic action of alpha-methylene lactones towards HeLa cells in culture

Possible targets to account for the qtotoxic activity of the a-methylene containing sesquiterpenes elephantopin and vernoleph, and an a-methylene-lactone steroidal derivative, 3-methoxy-16-methylene-17-oxo-17a-D homoestra-1,3,5,(10)-triene, have been studied. The compounds reduced surface and intracellular thiol levels in HeLa S3 ceb, caused an inhibition of Na+/K+-ATPase and an inhibition of the incorporation of [³H]thymidine into macromolecules. In addition, the steroidal compound, but not the sesquiterpene elephantopin, released lysosomal enzymes and caused marked changes in the structural integrity of the cells. Observed effects of α-methylene lactones on cellular respiration and [³H]thymidine uptake were not a consequence of alkylation. The results support the concept of the cell membrane and in particular Na⁺/K⁺-ATPase as a target for sesquiterpene lactone alkylation.