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Biomedical subjects

A J Popp

Publications and source records attributed to A J Popp.

At least 19 recordsLinked to original sources

Crossroads at Salerno: Eldridge Campbell and the writings of Theodorico Borgognoni on wound healing.

During Eldridge Campbell's tour of duty as the neurosurgical consultant to the Mediterranean theater of World War II operations, he was introduced to a then-revolutionary method of wound treatment. Ironically, Campbell's diligent research efforts later revealed that this method of wound treatment had first been advocated seven centuries earlier--in the same geographical location--by the Italian surgeon Theodoric. Although controversial, this method of wound care was subsequently applied and supported by Theodoric's outspoken pupil, Henri de Mondeville, despite intense opposition from the prevailing medical authorities who supported the doctrine of "laudable pus" for wound management. With Mondeville's death, Theodoric's technique lapsed into obscurity, relegated to a historical footnote until modern biology and the discoveries of Lister and Pasteur would again bring to light the benefits of nonsuppurative wound treatment. In this article the author discusses the work of Theodoric, Mondeville, and Campbell in light of the medical climate of their times and explores the contemporary parallels noted by Campbell in terms of the neglect of other, more recent medical discoveries. These examples encourage us to accept or reject medical treatments based on a thorough examination of their efficacy and not on the stature of their advocates within the medical community.

Debridement

Institutional Review Board evaluation of neuroscience protocols involving human subjects.

We analyzed our Institutional Review Board's (IRB) critiques of neuroscience protocols to identify areas of difficulty for investigators. Minutes from IRB meetings were reviewed, and criticisms were collated under applicable Code of Federal Regulations sections, coalescing into four categories: procedural issues, protocol critique, consent critique, and patient rights. Better communication with research subjects would have avoided a majority (66%) of criticisms. Procedural criticisms could have been reduced by adherence to IRB technical requirements. The small number of protocol design criticisms suggests either a lack of rigor in committee analysis or reliance on prior reviewers; it may also reflect the ongoing debate about the role of the IRB in evaluating scientific merit.

Clinical Protocols

Nerve entrapment and calf atrophy caused by a Baker's cyst: case report.

An unusual case of leg pain and atrophy in a patient with gastrocnemius due to tibial nerve branch compression by a Baker's cyst is presented. The clinical findings and electrodiagnostic studies were supportive of isolated medial gastrocnemius denervation. Treatment by synovectomy along with decompression of the branch of the posterior tibial nerve to the medial head of the gastrocnemius muscle resulted in clinical improvement. No other cases of such selective branch compression have been previously reported.

Follow-Up Studies

Continuous measurement of jugular venous oxygen saturation in response to transient elevations of blood pressure in head-injured patients.

Following traumatic brain injury, continuous jugular venous oxygen saturation (SjvO2) measurements have been made and used to assess cerebral oxygenation. Transients of SjvO2 may reflect cerebral blood flow (CBF) changes if measurements are made over a short period of time during which cerebral metabolic rate for oxygen is assumed unchanged. In response to alterations in perfusion pressure, transients of SjvO2 may indicate the extent to which autoregulation has been preserved after injury. The effect of arterial pressure changes on SjvO2 was measured in 14 severely head-injured patients (Glasgow Coma Scale score < 8) within 36 hours of injury. Mean arterial blood pressure (MABP), arterial oxygen saturation, and intracranial pressure (ICP) data were also continuously recorded by a computer at the patients' bedside. The reliability of the SjvO2 oximetry measurements varied among patients, and an average 38% of SjvO2 measurements were off by more than 6% saturation, necessitating recalibration. During periods of satisfactory catheter performance, 120 instances were found in which MABP was elevated more than 8 torr (mean +/- standard deviation: 32 +/- 13 torr) due to endotracheal suctioning. In 94 of these measurements, there was an associated increase in the ICP of 5 torr or more, averaging 16.6 +/- 10.2 torr. The SjvO2 was 0.62 +/- 0.10 before the increase in MABP and rose to a peak of 0.77 +/- 0.10 during the maximum MABP elevation, suggesting increased CBF during the transient hypertension. In 34 of 37 instances of persistent blood pressure elevations lasting for more than 10 minutes (mean 16.0 +/- 8.0 minutes), the SjvO2 elevation persisted (average duration 15.0 +/- 12.4 minutes), suggesting impaired or lost autoregulatory vasoconstriction. The presence or absence of hyperemia was unrelated to the extent of the autoregulation response. Results indicate that SjvO2 rises with increasing perfusion pressure during and after endotracheal suctioning, suggesting a feeble or absent autoregulatory response following traumatic brain injury.

Adolescent

Neurons of layer Vb of rat sensorimotor cortex atrophy but do not die after thoracic cord transection.

Albino rats six weeks (wk) of age underwent transection of the spinal cord at the level of the seventh thoracic vertebra. They were killed ten wk later by several schedules of formaldehyde-glutaraldehyde, formaldehyde and formaldehyde-ethanol-acetic acid perfusion-fixation. Layer Vb of the sensorimotor cortex, the site of origin of corticospinal axons severed by the operation, was searched by light and electron microscopic methods for evidence of neuronal necrosis. Cord-transected rats were compared with control, unoperated animals of identical age. Nerve cell death was not evident to qualitative study, although shrunken, deeply-staining neurons of artefactitious origin occurred capriciously in paraffin sections when fixation was initiated with a dilute formaldehyde-glutaraldehyde solution. Quantitative light and electron microscopic studies were also negative for indications of neuronal death. However, mild somal atrophy could be substantiated for layer Vb neurons of cord-transected rats by light microscopic, morphometric methods. Neuronal atrophy was unaccompanied by qualitative or quantitative ultrastructural alterations. Subcellular organelles and the per cent of neuronal plasma membrane apposed by axosomatic boutons were unchanged. Neuroglia and neuronal processes always had a normal electron microscopic appearance.

Animals

Duplex scanning of the internal carotid artery: an assessment of cerebral blood flow.

Duplex ultrasound scanning (B-mode imaging and pulsed Doppler shift analysis) was used to measure internal carotid artery blood flow (ICBF) in 20 volunteers. The effect of changes in end tidal CO2 on cerebral blood flow was measured. When corrected to a PCO2, of 40 torr (5.32 kPa) internal carotid artery blood flow was 286 +/- 16 ml min-1 (mean +/- s.e.m.). Specific CO2 reactivity (the change in flow per torr change in CO2) was 8.16 +/- 0.69 ml min-1 torr-1 which was equivalent to 2.0 +/- 0.1 per cent of the flow at 40 torr per torr change in CO2 (percentage CO2 reactivity). The mean value and the CO2 reactivity compare favourably with previously reported measurements by other techniques. These data suggest that the non-invasive measurement of internal carotid artery blood flow by Doppler ultrasound scanning is an assessment of cerebral blood flow that can be used to study both normal and pathological changes within the cerebral circulation.

Blood Flow Velocity

Improved recovery from a traumatic-hypoxic brain injury in cats by intracisternal injection of an anion transport inhibitor.

Cats, injured by a mechanical plus hypoxic model of traumatic brain injury, were treated by intracisternal injection of a modified loop diuretic (L-644,711). This drug inhibits the chloride/bicarbonate anion exchange transport system. The treatment resulted in a significant decrease in mortality from 61 to 21%, and an improvement in both neurological status and EEG activity of the surviving animals. The dose of drug given intracisternally was at least 175 times less than the dosage we previously found was needed to achieve a comparable effect when the drug was given intravenously. The present results suggest that certain types of head injury can be treated by drugs which affect cellular anion transport processes in the brain.

Animals

Glucose utilization is unchanged in red nucleus after axotomy.

Separate series of adult rats were subjected to unilateral high cervical and low thoracic section of the rubrospinal tract and sacrificed 1-30 (cervical series) and 3-100 days (thoracic series) later. Local cerebral glucose utilization ([14C]2-DG method of Sokoloff et al.) was determined in the red nucleus and in the inferior colliculus, nucleus interpositus and sensorimotor cortex of both sides in operates and controls. Although severe atrophy of rubral neurons follows cervical tractotomy while reversible chromatolytic alterations occur after thoracic lesions, glucose utilization did not differ in the red nucleus of operated and control rats. However, glucose utilization increased slightly in the inferior colliculus of all operated animals, a finding of indeterminate significance. The failure of axotomized intrinsic neurons of red nucleus and their surround to show altered glucose utilization stands in sharp contrast to the marked increase which occurs in cranial nerve nuclei after axotomy of their contained extrinsic neurons. The data are held to constitute another indication that there is a fundamental difference in the metabolic responses of extrinsic and intrinsic mammalian neurons to axotomy and may support the contention that, in mammals, the axon reaction of intrinsic neurons is fundamentally different from that of extrinsic nerve cells. This difference may have significance for failure of axon regeneration in mammalian CNS.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Agents for the treatment of brain injury. 1. (Aryloxy)alkanoic acids.

Blunt and ischemic injuries of the brain have been shown to result in swelling that is predominantly limited to a single cell type, the astrocyte, within the complex cellular mosiac of cerebral gray matter. Evaluation of various diuretic (aryloxy)acetic acids in vitro using incubating cat brain slices and primary astrocyte cultures identified compounds with marked ability to inhibit brain tissue swelling. Some of the compounds significantly reduced the mortality and morbidity following acceleration/deceleration brain injury in anesthesized cats. A variety of (indanyloxy)alkanoic acids were synthesized which were analogous to the dually active (indanyloxy)acetic acids. Some of the 4-(indanyloxy)butanoic acids were found to be devoid of diuretic activity but to possess equal or greater activity than the dually active compounds in the in vitro and in vivo brain assays. Selected examples from both the (indanyloxy)acetic and 4-(indanyloxy)butanoic acid series showed marked chiral effects, with one enantiomer generally exhibiting a much greater activity than the other. A clinical study of severely head-injured patients treated with ethacrynic acid demonstrated a significantly improved outcome when compared to controls. These data suggest a clinical advantage for the nondiuretic (aryloxy)alkanoic acids which possess in vitro and in vivo activities in the cat brain assays that are comparable or superior to dually active compounds.

Animals

Delayed pulmonary dysfunction in head-injured patients.

Intracranial pressure (ICP), cardiopulmonary function, and the degree of neurological dysfunction were measured in 13 patients with serious head injury to determine the relationship of these indices to the development of delayed pulmonary dysfunction. All patients had serious isolated head injury with Glasgow Coma Scale scores of 7 or less 6 hours after injury and elevated ICP at the time of admission to the protocol. Three patients developed arterial pO2 of less than or equal to 80 torr despite the initiation of elevated inspired oxygen fraction (FIO2 greater than or equal to 0.5) and positive end expiratory pressure (greater than or equal to 5 cm H2O. One of these three patients had a decline in neurological function, quantified by the Albany Head-Injury Watch Sheet, associated with hypoxemia. The only patients who developed intrapulmonary shunt fractions of more than 15% were five patients who had increased pulmonary vascular resistance (PVR) and elevated or increasing cardiac index, suggesting persistent perfusion to areas of the lung which normally are hypoperfused due to hypoxic pulmonary vasoconstriction. This mismatching of the distribution of ventilation and perfusion was confirmed using the multiple inert gas elimination technique in two patients with an increased shunt fraction. Unperfused gas exchange units were also found to be present, as confirmed by an abnormal multiple inert gas elimination techniques, high PVR and dead space/tidal volume ratio (VD/VT), and low extravascular lung water. Abnormalities of ICP and cerebral perfusion pressure could not be correlated with changes in any of the cardiopulmonary functions studied.

Adolescent

Adenosine-stimulated astroglial swelling in cat cerebral cortex in vivo with total inhibition by a non-diuretic acylaryloxyacid derivative.

The intact cerebral cortices of cats were exposed in vivo under normothermic conditions and superfused with isotonic artificial cerebrospinal fluid containing added 0.125 mM adenosine. This resulted in chloridecation-rich cerebrocortical swelling which was shown by electron microscopy to be associated with an expanded astroglial compartment. The addition of DCPIB, a non-diuretic acylaryloxyacid analogue of ethacrynic acid and an inhibitor of coupled chloride-cation transport in cerebral cortex in vitro, totally blocked astroglial swelling and the concomitant increases in tissue ion contents. These studies support our previous experiments on the mechanism of formation of astroglial swelling. The pathological consequences of astroglial swelling and the clinical applications of these findings are discussed.

Adenosine

Biology of glial swelling in experimental brain edema.

Most studies of clinically relevant cerebral edema emphasize the effect of added tissue fluid in white matter on gross distortion with transtentorial and subfalcine brain herniation. Our recent studies on altered tissue fluid compartmentation in cerebral gray matter suggest that significant microdistortion of relationships of capillaries to subserved tissue follows swelling of astroglia therein. Grave consequences to solute and gas exchange in focal regions may well be expected and are emphasized. The elucidation of the mechanisms of formation and inhibition of astroglial swelling by chemical agents, including chemically useful acylaryloxyacetic acid derivatives, are discussed. Furthermore, the effect of these agents in altering mortality and morbidity in a controlled, random study of animal head injury is presented.

Animals