Changes over time in thresholds for electrical stimulation of the cochlea

The purpose of this paper is to better characterize changes over time that occurred in psychophysical detection thresholds for electrical stimulation of the cochlea. Threshold changes observed in nonhuman primates implanted with cochlear electrode arrays can be divided into at least three types based on the patterns of change over time. Short-term increases and subsequent decreases in threshold were commonly observed during the first months after implantation and were often followed by periods of long-term threshold stability. Long-term slow increases in thresholds and more rapid increases after a period of threshold stability have also been observed. The threshold changes may be divided into at least two classes based on their dependence on the waveforms used for the threshold measurements. Some changes occurred primarily in thresholds for long phase-duration signals while other changes were equal in magnitude (in decibels) for all tested stimuli. This suggests that at least two mechanisms underlay these threshold changes. The observed changes in thresholds have implications for experimental studies of electrical stimulation and for clinical application of auditory prostheses.     

Physiology of alfentanil-induced rigidity

The authors investigated the hemodynamic, metabolic, electroencephalographic (EEG), and electromyographic (EMG) characteristics of narcotic-induced rigidity during induction of anesthesia with alfentanil (175 micrograms/kg) in 10 patients. Thiopental (4 mg/kg) was administered to a ten-patient control group. Rigidity was quantified in eight muscle groups (sternocleidomastoid, deltoid, biceps, forearm flexors, intercostal, rectus abdominus, vastus medialis/lateralis, and gastrocnemius). Marked rigidity was observed in all muscle groups in all patients receiving alfentanil and in none receiving thiopental. Central venous pressure increased with onset of rigidity, while mean arterial pressure and cardiac index remained unchanged. Manual ventilation was extremely difficult during alfentanil-induced rigidity. Arterial oxygen tension decreased more rapidly during rigidity than during the same time interval in the control group, while patients experiencing rigidity were more acidotic, as reflected by greater increases in base deficit. The EEG demonstrated an anesthetic state without seizure activity. The immediate increase in central venous pressure with the onset of rigidity, along with occasional simultaneous parallel variations in central venous pressure and the EMG, strongly suggest a mechanical mechanism for the change in central venous pressure. The metabolic changes during rigidity may be partly related to the absence of the normal cardiovascular reflexes that are reported to occur during voluntary isometric muscle contractions. A neurochemical mechanism of narcotic-induced rigidity is briefly reviewed.     

Enhanced G2 chromatid radiosensitivity, an early stage in the neoplastic transformation of human epidermal keratinocytes in culture

A deficiency in DNA repair, manifest as enhanced chromatid radiosensitivity during the G2 phase of the cell cycle, together with a proliferative stimulus such as that provided by active oncogenes may be necessary and sufficient for the malignant neoplastic transformation of human keratinocytes in culture. Normal epidermal keratinocytes established as continuous cell lines by transfection with pSV3-neo or infection with adeno 12-SV40 hybrid virus developed enhanced G2 chromatid radiosensitivity after 18 passages in culture. In contrast to cells from primary or secondary culture, these cells could be transformed to malignant neoplastic cells by infection with Kirsten murine sarcoma virus containing the Ki-ras oncogene or in one line by the chemical carcinogen, N-methyl-N'-nitro-N-nitrosoguanidine; both of these agents produced a marked proliferative response. Cytological heterogeneity and karyotypic instability characterized the cells during their progression to neoplasia. These results are interpreted in terms of a mechanism for neoplastic transformation.