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Biomedical subjects

B L Grundy

Publications and source records attributed to B L Grundy.

At least 19 recordsLinked to original sources
PubMed1997

Pharmacokinetics and pharmacodynamics of enantiomers of ibuprofen and flurbiprofen after oral administration.

The main objective of this study was to develop a pharmacokinetic-pharmacodynamic (PK/PD) model for the analgesic effect of ibuprofen and flurbiprofen using subjective as well as objective parameters. Serum concentrations of the individual enantiomers after oral administration of racemic ibuprofen (400 mg) and flurbiprofen (100 mg) were monitored using reversed phase HPLC. The pharmacokinetic data of the S-enantiomer was linked to the effect data using a hypothetical effect compartment. The effect data were fitted to Emax model. PK/PD analysis were performed using both objective (evoked potentials) and subjective (pain intensity scale) parameters. Concentrations of S-ibuprofen were found to be consistently larger than of R-ibuprofen and differed in various pharmacokinetic parameters after oral administration of racemic ibuprofen. Pharmacokinetic parameters of the enantiomers of flurbiprofen, such as volume of administration and clearance, also differed. Comparison of cumulative effects calculated as the area under the effect-time curve (AUCE) showed a statistically significant difference from placebo for both ibuprofen and flurbiprofen using evoked potential values. However, using pain rating values ibuprofen AUCE did not differ statistically significant from placebo whereas flurbiprofen AUCE did. PK/PD modeling of both evoked potentials and pain rating data than in evoked potential data. Hence, EP monitoring may allow to evaluate analgesic activity with a smaller number of subjects than pain rating.

Administration, Oral↗
PubMed1996

Pharmacodynamic evaluation of codeine using tooth pulp evoked potentials.

Pain assessment in human volunteers is difficult, and it often requires a large number of subjects to show analgesic efficacy with statistical significance. Electrical tooth pulp stimulation elicits a painful sensation and produces an electroencephalographic (EEG) signal that can be recorded from the scalp when precisely controlled dental stimuli are delivered. These somatosensory evoked potentials (EP) consist of a series of peaks or waves each characterized by their polarity, latency, and amplitude. They are obtained by processing the EEG signals that occur after tooth pulp stimulation. There is good correlation between subjective pain reports and evoked potential amplitudes (N150-P250 component). Thus, EP may provide a useful model for the assessment of analgesic activity in human volunteers. We describe an improved method for producing and recording tooth pulp evoked potentials in six healthy subjects. Only 16 EEG epochs were necessary to get a reproducible EP response from the participants. The approach was applied to study the efficacy of codeine (60 mg administered orally); a decrease in the evoked potential amplitudes after codeine administration was observed. The data were consistent with results from visual analog pain ratings given by the subjects.

Adult↗
PubMed1996

Metabolism of dynorphin A1-13 in human CSF.

In-vitro incubation of human cerebrospinal fluid (CSF) obtained from patients ranging from 22-78 years with 10 microM of dynorphin A1-13 (Dyn A1-13) resulted in several cleavage products. Dyn A1-12 and A2-13 were identified as the major CSF metabolites by matrix-assisted laser desorption mass spectrometry (LD-MS). Further metabolites were Dyn A1-6, A2-12 and A4-12. LD-MS further suggested the formation of Dyn A1-8, A1-7, A1-10, A7-10, A3-12, A7-12, A3-13, A7-13 and A8-13. The metabolic half-life of Dyn A1-13 at 37 degrees C was approximately 2.5 h (range 1.75-8.5 h), compared to less than one minute in plasma. The half-life of Dyn A1-13 decreased markedly with age or age-associated processes (n = 20, r2 = 0.498). Noncompartmental kinetic analysis in the absence or presence of enzyme inhibitors (leucinethiol 10 microM, captopril 100 microM and GEMSA 20 microM) suggested that Dyn A1-13 is mainly metabolized by carboxypeptidase to A1-12 (51%) and by aminopeptidases to A2-13 (35%). The generation of A1-6 (13%) was only detected under enzyme inhibition. The extent of conversion into the main metabolites did not follow an age-associated trend, thus over-all enzyme levels but no specific enzymatic systems are elevated with age.

Adult↗
PubMed1987

Monitoring of sensory evoked potentials is highly reliable and helpful in the operating room.

Because short-latency evoked potentials are relatively resistant to anesthetic agents, they can be used to monitor neural pathways during surgical procedures. The use of median nerve somatosensory evoked potentials to localize the central sulcus is an established aid of indisputable value in neurosurgical procedures involving cortical incisions for resection of certain epileptic foci, vascular malformations, or neoplasms near the central area of the brain. Likewise, recording of intraoperative nerve action potentials is currently regarded as indispensable in management of the neuroma-incontinuity after peripheral nerve trauma, as this evoked potential monitoring technique provides the only reliable method of distinguishing between axonotmetic and neurotmetic lesions. Evoked potential monitoring has been of value during many other types of surgical procedures, including cerebral aneurysm clipping, carotid endarterectomy, aortic procedures, microvascular decompression for trigeminal neuralgia and hemifacial spasm, acoustic neuroma resection, and a variety of spinal procedures. A detailed review of the literature is presented on the use of evoked potential monitoring for one of the more common indications: scoliosis surgery. Many orthopedic surgeons use the "wake-up test" only if the somatosensory evoked potentials change during surgery. A detailed review of the few reported cases of "false negative" evoked potentials is presented. The dearth of convincing reports of such phenomena in the face of so many positive experiences should persuade even the skeptical that monitoring of evoked potentials is a highly reliable and helpful intraoperative tool.

Brain Mapping↗
PubMed1987

Characteristics of nurse anesthetists working with and without anesthesiologists.

All professionally active certified registered nurse anesthetists (CRNAs) in four geographically representative states were surveyed by mail and telephone in 1981, and response rate of greater than or equal to 70% was obtained for each state. CRNAs who worked with anesthesiologists (Group I) were compared with those who worked in hospitals with no anesthesiologists (Group II). More than 75% of both groups were employed by hospitals, but Group II CRNAs (15.5% of respondents) were nearly five times as likely to practice on an independent, fee-for-service basis. Members of Group II worked predominantly in hospitals in small or rural communities and, compared with those in Group I, were more likely to be male and older, less likely to hold a baccalaureate degree, and less likely to use invasive monitoring techniques. Nearly 50% of Group II had no standing consulting relationship with an anesthesiologist. A consultation network supported by telecommunications deserves consideration as a means of providing CRNAs who work independently in small rural hospitals with a cost-effective team approach to anesthesia care.

Adult↗
PubMed1987

Electrophysiological evaluation of the patient with acute spinal cord injury.

This article reviews basic principles, equipment and techniques, and clinical applications of electrophysiologic monitoring in patients with spinal cord injuries. Four groups of electrophysiologic measurements are considered: Somatosensory evoked potentials (SEPs); motor evoked potentials (MEPs); electromyography (EMG) and nerve conduction studies; and late responses, including H reflex, M response, and F wave. Reports of SEP recordings in spinal cord injury, as drawn from the literature, are tabulated in detail.

Electromyography↗
PubMed1985

EEG changes during carotid endarterectomy: drug effect and embolism.

Clinical neurological status and the electroencephalogram (EEG) were monitored during right carotid endarterectomy under regional anaesthesia in a patient who had suffered two prior cerebral infarctions. No change in EEG or clinical status was seen with occlusion of the carotid artery, but generalized encephalopathic changes were seen after a small dose of narcotic given before carotid occlusion. Bihemispheric changes in EEG and neurological status occurred upon release of carotid occlusion. This case demonstrates three important points. First, EEG changes can be seen with sedative or anaesthetic agents in patients who have previously suffered brain injury. Second, temporary neural dysfunction may be seen remote from the site of a localized injury to the brain--a phenomenon known as diaschisis. Finally, this report reiterates the observation that the risk of injury to the brain during carotid endarterectomy is not limited to the period of possible ischaemia during occlusion of the carotid artery.

Aged↗
PubMed1982

Deliberate hypotension for spinal fusion: prospective randomized study with evoked potential monitoring.

Twenty-four patients requiring spinal fusion with Harrington rod instrumentation were studied prospectively to determine the effects of moderate hypotension on blood loss, operating conditions, operating time and spinal cord function. Hypotension reduced blood loss and improved operating conditions but did not shorten operating time. Five patients had alterations in somatosensory cortical evoked potentials after straightening of the spine that prompted us to reverse hypotension (when present) and haemodilution, and then to do wake-up tests. All wake-up tests were normal and all evoked potential alterations resolved during operation. Hypotension seems unlikely to increase the risk of neurological damage if spinal cord function is monitored. Our findings suggest that patients subjected to spinal fusion need not be awakened during operation for testing of cord function provided somatosensory evoked potentials are monitored and remain stable.

Adolescent↗
PubMed1982

Carotid endarterectomy under regional (conductive) anesthesia.

Carotid endarterectomy is reliable in the prevention of strokes due to arteriosclerotic disease at the carotid bifurcation. This is a retrospective review of 314 carotid endarterectomies performed at the University Health Center of Pittsburgh. The objectives of the study were to determine if regional anesthesia was a safe technique for carotid endarterectomy and to determine whether the neurologic complications that occurred were embolic or ischemic in origin. In patients who were neurologically intact before operation, the perioperative mortality was 0.88% and the incidence of neurologic complications was 3.1%. This is comparable to the current literature. Observations of the awake patient suggested that half the neurologic deficits that occurred in this series were due to embolization rather than to cerebral ischemia. Further more, the incidence of non-neurologic complications under general anesthesia was 12.9%. Under regional anesthesia, the incidence of non-neurologic complications was 2.8%. The data supports carotid endarterectomy under regional block as safe and reliable method.

Anesthesia, Conduction↗
PubMed1982

Telemedicine in critical care: problems in design, implementation, and assessment.

We introduced telemedicine, i.e., telecommunications for delivery of health services, to alleviate scarcity and maldistribution of critical care services. For 18 months, we used interactive television to provide consultation with university-based critical care physicians for patients in the ICU of a 100-bed hospital. Telemedicine "visits" (1548) were made to 395 patients. Television consultation had greater clinical and educational impact than consultation using the telephone. Equipment was expensive but proved to be reliable and easy to use. Interactive television extended the availability of specialist expertise, but full exploitation of this technology for delivery of critical care services was not achieved. Extensive background research, currently underway at the University of Pittsburgh, is necessary before the next telemedicine demonstration.

Critical Care↗
PubMed1982

Evoked potential changes produced by positioning for retromastoid craniectomy.

Reversible changes in brain stem auditory evoked potentials (BAEPs) occurred in a patient with hemifacial spasm when she was positioned for retromastoid craniectomy. The peak latencies increased and the amplitudes decreased. These alterations persisted for 3 hours, but returned immediately toward normal when the head was removed from pin fixation and the neck was returned to a neutral position. Similar BAEP changes were documented during a second procedure. Audiograms were normal pre- and postoperatively, although minimal BAEP changes were seen after operation. Our observation sheds light on possible mechanisms of intraoperative BAEP alteration and provides new information about the degree and duration of intraoperative BAEP distortion that can be tolerated in at least some cases without permanent neurological sequelae.

Brain Stem↗