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Biomedical subjects

S R Hameroff

Publications and source records attributed to S R Hameroff.

At least 19 recordsLinked to original sources
PubMed1994

Quantum optical coherence in cytoskeletal microtubules: implications for brain function.

'Laser-like,' long-range coherent quantum phenomena may occur biologically within cytoskeletal microtubules. This paper presents a theoretical prediction of the occurrence in biological media of the phenomena which we term 'superradiance' and 'self-induced transparency'. Interactions between the electric dipole field of water molecules confined within the hollow core of microtubules and the quantized electromagnetic radiation field are considered, and microtubules are theorized to play the roles of non-linear coherent optical devices. Superradiance is a specific quantum mechanical ordering phenomenon with characteristic times much shorter than those of thermal interaction. Consequently, optical signalling (and computation) in microtubules would be free from both thermal noise and loss. Superradiant optical computing in networks of microtubules and other cytoskeletal structures may provide a basis for biomolecular cognition and a substrate for consciousness.

Animals↗
PubMed1993

Cytoskeletal logic: a model for molecular computation via Boolean operations in microtubules and microtubule-associated proteins.

Adaptive behaviors and dynamic activities within living cells are organized by the cytoskeleton: intracellular networks of interconnected protein polymers which include microtubules (MTs), actin, intermediate filaments, microtubule associated proteins (MAPs) and other protein structures. Cooperative interactions among cytoskeletal protein subunit conformational states have been used to model signal transmission and information processing. In the present work we present a theoretical model for molecular computing in which Boolean logic is implemented in parallel networks of individual MTs interconnected by MAPs. Conformational signals propagate on MTs as in data buses and in the model MAPs are considered as Boolean operators, either as bit-lines (like MTs) where a signal can be transported unchanged between MTs ('BUS-MAP'), or as bit-lines where a Boolean operation is performed in one of the two MAP-MT attachments ('LOGIC-MAP'). Three logic MAPs have been defined ('NOT-MAP, 'AND-MAP', 'XOR-MAP') and used to demonstrate addition, subtraction and other arithmetic operations. Although our choice of Boolean logic is arbitrary, the simulations demonstrate symbolic manipulation in a connectionist system and suggest that MT-MAP networks can perform computation in living cells and are candidates for future molecular computing devices.

Animals↗
PubMed1989

Transdermal fentanyl: pharmacokinetics and preliminary clinical evaluation.

A new transdermal drug-delivery system that administers the synthetic opioid fentanyl through intact skin was evaluated for 24 hours postoperatively in eight patients who had undergone orthopedic surgery. Plasma samples were obtained over a 72-hour period for pharmacokinetic analysis in five patients. The patients were also evaluated intensively for adequacy of analgesia, frequency of nausea and sedation, and occurrence of ventilatory depression. A median lag time of 2.25 hours after application of the transdermal system was observed before the appearance of fentanyl in the blood. Median peak concentration and time to peak were 1.0 ng/ml and 22 hours, respectively. The apparent elimination of fentanyl after transdermal administration is prolonged relative to previously reported values. Absorption analysis indicates zero-order fentanyl administration, and in addition, suggests deposition of drug in an epidermal site, with the resultant prolonged absorption process giving the appearance of slow elimination. No significant toxicities were observed. Four patients required no additional analgesia. No consistent correlations among fentanyl concentration and any clinical values were observed. Transdermal administration of fentanyl appears to be a viable alternative to conventional routes of narcotic administration and warrants further study.

Absorption↗
PubMed1988

Phase space electroencephalography (EEG): a new mode of intraoperative EEG analysis.

Intraoperative monitoring of electroencephalography (EEG) data can help assess brain integrity and/or depth of anesthesia. We demonstrate a computer generated technique which provides a visually robust display of EEG data plotted as 'phase space trajectories' and a mathematically derived parameter ('dimensionality') which may correlate with depth of anesthesia. Application of nonlinear mathematical analysis, used to describe complex dynamical systems, can characterize 'phase space' EEG patterns by identifying attractors (geometrical patterns in phase space corresponding to specific ordered EEG data subjects) and by quantifying the degree of order and chaos (calculation of dimensionality). Dimensionality calculations describe the degree of complexity in a signal and may generate a clinically useful univariate EEG descriptor of anesthetic depth. In this paper we describe and demonstrate phase space trajectories generated for sine waves, mixtures of sine waves, and white noise (random chaotic events). We also present EEG phase space trajectories and dimensionality calculations from a patient undergoing surgery and general anesthesia in 3 recognizable states: awake, anesthetized, and burst suppression. Phase space trajectories of the three states are visually distinguishable, and dimensionality calculations indicate that EEG progresses from 'chaos' (awake) to progressively more 'ordered' attractors (anesthetized and burst suppression).

Electroencephalography↗
PubMed1988

STM imaging of molecular collagen and phospholipid membranes.

The application of STM to biological materials has been limited by poor conductivity, sample geometry and stability of biological materials. In this paper we describe an STM study of the monomeric helical forms of collagen, a stable, conductive and widely prevalent structural protein. We have also used STM to image artificial Langmuir DPE (dipalmitoyl phosphatidyl ethanolamine) phospholipid membranes. Both molecular collagen and the phospholipid membranes were dried in air on highly oriented pyrolytic graphite (HOPG). Our STM images of collagen dried on HOPG reveal strands 15 A in diameter with a periodicity of about 30 A which correlates with that known to occur in collagen. Spikes which periodically protrude from strands in our STM images of collagen appear to represent pyrrolidine ring structures in the amino acids proline and hydroxyproline. Thus, we report the first STM imaging of native biomolecules revealing intramolecular details and what appear to be specific amino acids. STM imaging of phospholipid membranes show a lattice pattern with densities spaced approximately 4.5 A apart. These are thought to represent individual phospholipid molecules in an artificial membrane formed on the HOPG. We believe STM and its related technologies will have great future utility in biomolecular studies.

Animals↗
PubMed1987

Effect of alterations in frequency, inspiratory time, and airway pressure on gas exchange during high frequency jet ventilation in dogs with normal lungs.

High frequency jet ventilation (HFJV) is becoming increasingly useful for providing respiratory support in patients with normal lungs during operative procedures, and also has been advocated as a technique for ventilating patients during cardiopulmonary resuscitation. We studied the effect of frequency, percent inspiratory time (I/E ratio), peak airway pressure, and airway pressure difference (peak-PEEP) during HFJV as operational variables on the efficacy of gas exchange in dogs with normal lungs. We observed that at a constant peak airway pressure and percent inspiratory time, PaCO2 generally increases as frequency rises above 100/min. In contrast, PaCO2 generally decreases as percent inspiratory time is reduced at a constant frequency and peak airway pressure. In addition, increasing peak airway pressure and airway pressure difference are associated with lower levels of PaCO2. Arterial oxygenation was adversely affected by frequencies above 300/min, but was otherwise not influenced by alterations in frequency, percent inspiratory time, or airway pressure.

Animals↗
PubMed1986

Effects of pulse duration on neuromuscular blockade monitoring: implications for supramaximal stimulation.

Questions have been raised concerning the reliability of surface electrodes in achieving supramaximal stimulation during the monitoring of neuromuscular blockade; needle electrodes are considered reliable in this respect. This study compares interelectrode impedances of needle and surface electrodes during neuromuscular blockade monitoring and suggests those characteristics of the stimulation pulse that can ensure reliable supramaximal stimulation with either type of electrode. Interelectrode voltage and current for surface and needle electrodes were measured by using 1.0-ms pulses at low, medium, and high stimulation levels on 22 surgical patients during anesthesia. Data were collected immediately after electrode application, and again at 10 minutes after application. Stimulation with surface electrodes produced an initial, transient surge of current, followed by a lower steady-state value. At high stimulation levels, the peak transient current was 87% higher than the steady-state current. Needle electrodes produced a constant high-current response. At high stimulation levels the transient impedance of the surface electrode and the impedance of the needle electrode were essentially equal (0.7 k omega and 0.75 k omega, respectively). The transient impedance was significantly lower (P less than 0.001) and was associated with less interpatient variation (P less than 0.001) and less sensitivity to the duration of electrode application than was the steady-state impedance of the surface electrode. These data suggest that high-current pulses with widths of less than 0.2 ms could provide reliable supramaximal stimulation with either type of electrode.

Electric Conductivity↗
PubMed1986

Effect of hyperbaric oxygen therapy or dimethyl sulfoxide on cerebral ischemia in unanesthetized gerbils.

To determine whether treatment with hyperbaric oxygen (HBO) or dimethyl sulfoxide (DMSO) could mitigate the fatal effects of cerebral ischemia, we anesthetized 68 gerbils with ketamine, ligated the right carotid artery (CA), and placed a snare occluder around the left CA. After 48 hours, 30 gerbils that were neurologically normal or had suffered only mild deficits were subjected to left CA occlusion without anesthesia for periods of 2 to 60 minutes. The onset of circling, posturing, falling, and lethargy began immediately; seizures and coma ensued 4 to 5 minutes later and persisted until release of the left CA occluder. All gerbils recovered after 2-minute staged bilateral CA occlusions. The mortality rate was 33% after both 5- and 10-minute occlusions and 100% after 20- and 60-minute bilateral occlusions. Twelve gerbils were placed in an HBO chamber (100% oxygen at 1.5 atmospheres) for 15 minutes during 20-minute bilateral occlusion; only 2 died (16% mortality rate). Thus, HBO therapy conferred significant protection against death from untreated ischemia (P less than 0.001). Histological examination showed that the extent of patchy bilateral ischemic neuronal damage was much less in surviving gerbils that received HBO therapy than in those that died after 20-minute occlusions. Fourteen gerbils were treated with DMSO, 2.5 g/kg intraperitoneally, during 5- or 10-minute bilateral CA occlusion; 12 died (86% mortality rate). Thus, DMSO provided no protection against fatal cerebral infarction; in fact, the results in the 10-minute reperfusion group suggest that DMSO may have a deleterious effect.

Animals↗
PubMed1985

Effects of halothane and fentanyl anesthesia on plasma beta-endorphin immunoreactivity during cardiac surgery.

We studied the effects of halothane anesthesia (n = 6) and fentanyl anesthesia (n = 9; 50-100 micrograms/kg) on plasma beta-endorphin immunoreactivity as a measure of stress response during coronary artery bypass grafting, including cardiopulmonary bypass. Plasma levels of beta-endorphin immunoreactivity measured prior to induction, after induction, after intubation, after skin incision, during cardiopulmonary bypass, and on leaving the operating room were significantly higher in patients given halothane during cardiopulmonary bypass and on leaving the operating room than they were in patients given fentanyl.

Anesthesia↗
PubMed1984

Evaluation of peripheral nerve stimulators and relationship to possible errors in assessing neuromuscular blockade.

Voltage and current output characteristics were measured on six commercially available peripheral nerve stimulator devices. The results are evaluated as possible sources of variability in peripheral nerve stimulator function and neuromuscular blockade assessment. The authors found significant differences in output voltage waveform and in maximum current into a 470 ohm load (21.4 to 128 mA.). Output current decreased from 25 to 88% in the different devices, with a load impedance increase from 470 to 10,000 ohms. Due to the variability in peripheral nerve stimulation units and the decrease in current output at higher load impedance, less than supramaximal stimulation is possible with erroneous interpretation of neuromuscular blockade.

Electric Stimulation↗
PubMed1984

Airway movement in dogs during high-frequency jet ventilation.

Cine tantalum bronchograms were recorded from 7 pentobarbital-anesthetized dogs during spontaneous ventilation (SV), high-frequency jet ventilation (HFJV) at 3 frequencies, and intermittent positive-pressure ventilation (IPPV) at 3 combinations of tidal volume (VT) and rate. During SV and the 3 IPPV conditions, the percent inspiratory increase in the diameter of airways greater than 3 mm was the same as in airways less than 3 mm. With HFJV, the percent increase in the diameter of airways greater than 3 mm was twice that of smaller airways. Increases in airway diameter are proportional to transmural, and hence intraluminal airway pressure. These data, therefore, indicate that the contribution of intraluminal pressure changes to intrapulmonary gas transport in small airways during HFJV is less than with either SV or IPPV, and that mechanisms responsible for intrapulmonary gas transport in small conducting airways during HFJV are different than those associated with either SV or IPPV.

Air Movements↗
PubMed1984

Fentanyl preloading for rapid-sequence induction of anesthesia.

Protecting the patient's airway is of paramount importance in the induction of general anesthesia. For the patient at risk of regurgitation of stomach contents, the rapid-sequence (crash) induction provides protection, but at the expense of increased stress response to laryngoscopy and intubation. This stress response is especially dangerous for the patient at risk for myocardial ischemia. The purpose of this study was to examine the efficacy of using low-dose fentanyl (5 micrograms/kg) to reduce cardiovascular and neuroendocrine stress responses to rapid-sequence induction. Thirty patients were randomly assigned to a rapid-sequence induction protocol either with or without fentanyl preloading. Fentanyl-preloaded patients (fentanyl group) received 2 mg/kg of thiopental whereas patients who were not preloaded with fentanyl (control group) received 4 mg/kg of thiopental. Data collected as indices of the stress response included heart rate, systolic, diastolic, and mean blood pressures, and plasma concentrations of catecholamines (epinephrine, norepinephrine, dopamine) and beta-endorphin. Electrocardiograms (modified V5 lead) were monitored for dysrhythmias and ST segment depression. Control patients had higher systolic, diastolic, and mean blood pressures after intubation than did patients given fentanyl (P less than 0.05). Although the incidence of dysrhythmias was decreased by fentanyl (20% vs 42%), this difference was not statistically significant. Plasma concentrations of beta-endorphin and norepinephrine increased significantly in control patients but not in patients given fentanyl (P less than 0.05). Low-dose fentanyl (5 micrograms/kg) reduces some aspects of the stress response to rapid-sequence induction of anesthesia.

Adult↗
PubMed1984

Doxepin's effects on chronic pain and depression: a controlled study.

Sixty patients with chronic pain of the low back or cervical spine concomitant with clinical depression were studied in a 6-week, randomized, double-blind comparison of doxepin and placebo. Significant improvements in the doxepin-treated group compared to placebo or to baseline values were seen on Hamilton depression scores, Global Assessment Scale scores, pain severity, percent of time pain felt, and effect of pain on activity, sleep, and muscle tension. Some improvements were observed after 1 week of treatment; the most improvement occurred at 6 weeks, when the mean doxepin dosage was approximately 200 mg/day and plasma doxepin and nordoxepin averaged 80 ng/ml. No significant harmful effects were observed. Neither plasma beta-endorphin nor enkephalin-like activity demonstrated significant differences from baseline. These data indicate that doxepin is a valuable treatment for patients with chronic pain and depression.

Chronic Disease↗