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Biomedical subjects

R M Davidson

Publications and source records attributed to R M Davidson.

At least 19 recordsLinked to original sources

Description of an in vitro platelet function analyzer--PFA-100.

A new in vitro system for the detection of platelet dysfunction, PFA-100, has been developed. It provides a quantitative measure of platelet function in anticoagulated whole blood. The system comprises a microprocessor-controlled instrument and a disposable test cartridge containing a biologically active membrane. The instrument aspirates a blood sample under constant vacuum from the sample reservoir through a capillary and a microscopic aperture cut into the membrane. The membrane is coated with collagen and epinephrine or adenosine 5'-diphosphate. The presence of these biochemical stimuli, and the high shear rates generated under the standardized flow conditions, result in platelet attachment, activation, and aggregation, slowly building a stable platelet plug at the aperture. The time required to obtain full occlusion of the aperture is reported as the "closure time." We have found that impairment of von Willebrand factor, or inhibition of platelet receptors glycoprotein Ib or IIb/IIIa with monoclonal antibodies or peptides, resulted in abnormal closure times. An antifibrinogen antibody, in contrast, failed to show any effect. The test appears to be sensitive to platelet adherence and aggregation abnormalities. The PFA-100 system has potential applications in routine evaluation of platelet function in the clinical setting because of its accuracy, ease of operation, and rapid turnaround of results.

Bleeding Time

Amyloid beta-peptide (A beta P) potentiates a nimodipine-sensitive L-type barium conductance in N1E-115 neuroblastoma cells.

The neurodegenerative pathology observed in Alzheimer's Disease (AD) has been partially attributed to the neurotoxic effects of the amyloid beta-peptide (A beta P), although the mechanisms underlying this neurotoxicity are unknown. Since A beta P is capable of forming cation channels in lipid bilayers, it is possible that the neurotoxic effects on neurons may be mediated by a cation flux. We have used patch-clamp recording techniques to study the effects of A beta P on cation currents in differentiated mouse N1E-115 neuroblastoma cells. In whole-cell recordings, incubation of cells with A beta P for 24 h significantly increased the median peak inward current from -201.8 pA to -352.0 pA, and shifted the voltage at peak current (Vpeak) and that of current activation (Vact) towards more positive potentials. For untreated cells, median Vpeak was 1.7 mV and Vact was -28.9 mV, vs. 10.5 mV and -24.7 mV in A beta P-treated cells. Incubation with the reverse sequence A beta P(40-1) or A beta P(25-35) did not produce significant changes in the amplitude or kinetic behavior of the inward current. At the single channel level, A beta P added to the pipette increased the open probability of cation-conducting ion channels. As determined by cell viability counts, both A beta P(1-40) and the A beta P(25-35) fragment had neurotoxic effects; within 24 h, addition of A beta P reduced the number of viable cells by more than 50%. It is suggested that the neurotoxic effects of A beta P may be mediated by its ability to form cation channels de novo and/or alter the activity of cation channels already present in the cell membrane.

Alzheimer Disease

Neural form of voltage-dependent sodium current in human cultured dental pulp cells.

Intradental, i.e. pulpal, cells may play an important part in sensory transduction in teeth, although the cellular mechanisms and the identity of the specific cell types involved are still unclear. Because the majority of cells in dental pulp are derived from neural crest, it seemed likely that these might have the membrane properties of other neural-derived cells found in the peripheral or central nervous system. The patch-clamp recording technique was used to show that cells in explant cultures from human dental pulp contain a voltage-gated, tetrodotoxin-sensitive inward current. Mean activation potential of the current was -42 +/- 2.5 mV and the voltage at half-inactivation was -79.4 +/- 5.3 mV, suggesting a neural-like sodium conductance. In addition, these cells were immunoreactive to glial acidic fibrillary protein, growth-associated protein (GAP-43), and vimentin, further suggesting that dental pulp contains a population of cells with membrane properties similar to neuronal satellite cells. These cells may contribute, either directly or indirectly, to somatosensation in teeth.

Adolescent

Membrane stretch activates a high-conductance K+ channel in G292 osteoblastic-like cells.

A high-conductance K(+)-selective ion channel was studied in excised membrane patches from human G292 osteoblast-like osteosarcoma cells. Channel conductance averaged approximately 170 pS in symmetric solutions of 153 mM KCl, and approximately 135 pS when the pipette was filled with standard saline (150 mM NaCl). The probability of the channel being in an open state (Popen) increased with membrane potential, internal calcium, and applied negative pressure. At pCa7, channel activity was observed at membrane potentials greater than approximately 60 mV, while at pCa3, channel activity was seen at approximately 10 mV. Likewise, in the absence of applied pressure, channel openings were rare (Popen = 0.02), whereas with -3 cm Hg applied pressure, Popen increased to approximately 0.40. In each case, i.e., voltage, calcium concentration, and pressure, the increase in Popen resulted from a decrease in the duration of long-closed (interburst) intervals and an increase in the duration of long-open (burst) intervals. Whole-cell responses were consistent with these findings. Hypotonic shock produced an increase in the amplitude and conductance of the outward macroscopic current and a decrease in its rise time, and both single-channel and whole-cell currents were blocked by barium. It is suggested that the voltage-gated, calcium dependent maxi-K+ channel in G292 osteoblastic cells is sensitive to membrane stretch and may be directly involved in osmoregulation of these cells. Further, stretch sensitivity of the maxi-K+ channel in osteotrophic cells may represent an adaptation to stresses associated with mechanical loading of mineralized tissues.

Calcium

Potassium currents in cells derived from human dental pulp.

Patch-clamp recording methods were used to monitor ion currents in tissue-cultured cells derived from human dental pulp. Recordings were made in excised, outside-in or whole-cell patches. In single-channel experiments, the majority of patches contained a high-conductance (approx. 140-180 pS) K(+)-selective ion channel. The probability of the channel being in an open state was dependent on membrane potential, internal calcium and negative pressure applied to the cell membrane. Whole-cell recordings were consistent with these findings; in response to step-wise depolarizations of the cell membrane, most displayed a family of outwardly rectifying, barium-sensitive currents. In addition, a number of patches contained a second class of potassium channel of intermediate (approx. 85-100 pS) conductance, which was largely voltage insensitive and independent of calcium concentration. These results suggest that pulp cells contain a high-conductance potassium channel which probably underlies the outwardly rectifying current found at the whole-cell level. Further, the existence of mechanosensitive channels in these cells raises the possibility that the response to mechanical perturbation of dental pulp may be mediated, in part, by direct effects on odontogenic cells.

Adolescent

Temporal changes in myocardial uptake on serial bone scans in two cases of presumed senile cardiac amyloidosis.

Two unusual examples of cardiac uptake in elderly patients who had received serial bone scans, one with a "waxing" and the other with a "waning" pattern of myocardial tracer uptake, are presented. An apparent temporal discordance between echocardiographic and scintigraphic findings is noted. Neither of the two patients had clinical, electrocardiographic, or other laboratory evidence of old or new myocardial infarction. Possible causes for the temporal changes are described. Presumptive diagnoses of senile cardiac amyloidosis were made based on clinical findings, noninvasive imaging, and comparison with a historic cohort at the Veterans Administration Medical Center in Houston.

Aged

Effect of corticotectal tract lesions on relative motion selectivity in the monkey superior colliculus.

Many cells in the superficial layers of the monkey superior colliculus are sensitive to the relative motion between a small target moving through the classic receptive field and a textured, moving background pattern that fills the visual field beyond the classic receptive field. The cells respond well when motion of the target differs from that of the background, but their responses are suppressed when the target moves in phase with the background. To determine whether this relative motion sensitivity depends on input to the colliculus from visual cortex, we studied colliculus cells in immobilized, anesthetized monkeys after unilateral thermocoagulation, or anesthetic blockade, of the corticotectal tract at the level of the pulvinar. In the colliculus ipsilateral to the corticotectal tract lesions, relative motion sensitivity was significantly reduced when compared either with the colliculus in intact animals or with the colliculus contralateral to the lesion. However, a moving-background stimulus still had a modest suppressive effect compared with a stationary background ("background motion sensitivity"), as is the case for intact animals. Anesthetic blockade of the corticotectal tract had similar effects; relative motion sensitivity, but not background motion sensitivity, was lost following injection of mepivacaine or bupivacaine. Pulvinar cell loss alone, induced by kainic acid injection, had no effect on relative motion sensitivity in the colliculus. The corticotectal tract lesions, but not the anesthetic injections, also had minor effects on flash-evoked responses and spontaneous discharge rates; these effects may reflect a retrograde response of some tectopulvinar cells to injury of their axons by the corticotectal tract lesions. In the colliculus opposite the corticotectal tract lesion, relative motion sensitivity was similar to that in normal animals. However, responses in the presence of a moving background were enhanced, suggesting that removal of cortical input to one colliculus may disinhibit the contralateral colliculus, a phenomenon reminiscent of the Sprague effect in the cat. We conclude that while cortical input to the colliculus may contribute little to the classic receptive field properties of superficial-layer cells, it clearly does contribute to relative motion sensitivity.

Anesthetics, Local

Selectivity for relative motion in the monkey superior colliculus.

1. Cells in the superficial layers of the colliculus were studied in immobilized monkeys anesthetized with nitrous oxide. We examined sensitivity to the relative motion between two stimuli: a small target in a cell's receptive field and a large random-dot background pattern that filled most of the visual field outside the receptive field. 2. Most cells were nonselective for either target direction or speed when the background pattern was stationary but were selective for both direction and speed relative to a moving background. Selectivity for relative motion was independent of the absolute direction and speed of both target and background. When both moved at the same speed in the same direction, the response evoked by the target was strongly suppressed. Changing the background direction relative to the target reduced the suppression; suppression was minimal when the two moved in opposite directions. Selectivity for relative direction was broad: the average tuning width at half-amplitude was 136 degrees. When target and background moved in the same direction, increasing or decreasing background speed relative to the target likewise reduced suppression. Average tuning width for relative speed was 1.4 log units. 3. Selectivity for relative motion was a global phenomenon. Suppression was present even when the background pattern was excluded from a region 10 times the receptive-field diameter. However, suppression gradually diminished with increasing distance between the receptive field and the background pattern. 4. Relative motion selectivity was most common in the deeper part of the superficial layers. Ninety percent of the cells below the middle of the stratum griseum superficiale were selective for relative direction, whereas above this level only 45% of the cells were. 5. Cells in the magnocellular and parvocellular layers of the lateral geniculate nucleus did not show selectivity for relative direction. 6. We suggest that the lower one-half of the superficial grey layer and the stratum opticum together constitute a subdivision of the superior colliculus that is specialized to detect strong discontinuities in relative motion. Descending input by way of the corticotectal tract is probably essential for the detection process. the projections from this tectal motion zone to the pulvinar, and from there to prestriate cortex, may provide a feedback pathway through which motion discontinuities such as occur at dynamic occlusion boundaries can influence local feature detection by cortical neurons.

Animals

Multiple forms of mechanosensitive ion channels in osteoblast-like cells.

Patch-clamp recording techniques were used to examine the direct effects of mechanical stimulation on ion channel activity in human osteoblast-like osteosarcoma cells. Three classes of mechanosensitive ion channels were present and could be distinguished on the basis of conductance, ionic selectivity, and sensitivity to membrane tension. The largest conductance channel (160 pS) was K(+)-selective and showed both a decrease in long closed interval duration and an increase in burst length with increasing membrane tension. For low applied pressures, there was an e-fold increase in the probability of this channel being open (Popen) for every 3.4 cm2 Hg change in pressure. Two additional pressure-dependent channels had smaller conductances, i.e., 60 pS and 20 pS; the 60 pS channel appeared to be non-selective for cations. We propose that one or more of these mechanosensitive channels is involved in the response of bone to mechanical loading.

Bone Neoplasms

Metastatic calcification in a patient with malignant parathyroid carcinoma. Correlation of clinical, surgical, radiographic, and scintigraphic findings.

A patient whose bone scan showed features typical of a "superscan," having extensive pulmonary, cardiac, and renal calcifications is described. Metastatic parathyroid carcinoma with renal insufficiency and phosphate retention are cited as the cause. Early diagnosis and surgical extirpation offer the best chance for cure or palliation. Pitfalls of plain film radiography in identifying metastases and pathologic soft tissue calcifications in the setting of severe hyperparathyroidism are discussed, and the advantages of functional radionuclide imaging assessments are emphasized.

Bone Neoplasms

Indium-111 WBC scan in acute toxic centrilobular hepatic necrosis.

In this case of prolonged fever and abnormal liver functions, dual tracer scintigraphy with In-111 WBCs and Tc-99m SC led to a biopsy-proven diagnosis of severe acute toxic hepatitis (hepatocellular necrosis). Correlation of the Tc-99m SC scan findings with those previously reported for "pseudotumors" of the liver is discussed. A "pseudonormal" scan pattern is described for the In-111 WBC scintigraphy. Discordance between In-111 WBC and Tc-99m SC scintigraphy in this clinical setting should raise the possibility of hepatic necrosis as a diagnostic alternative to hepatic abscess.

Adult

Schoolboy Rugby injuries, 1969-1986.

For 18 years (1969-1986) a casualty station has been operating during all Saturday interschool Rugby matches at a private school. Since its inception, both the diagnosis and the early management have been documented for every injury that presented to this station. Over this period, 1444 boys have been seen, of whom 116 sustained injuries that were classified as being severe; of these, only two injuries--a skull fracture and a fracture--dislocation of the cervical spine--were regarded as clinically serious. Over all, the injury rate was 176/10 000 player-hours, or 1.56/100 player-games; the rate of severe injury was 14/10 000 player-hours, or 0.12/100 player-games. Injury rates were highest in older boys and in those who were in the most advanced grades of play. Fullbacks experienced the most injuries; otherwise, little variation occurred in injury rates by player position. No consistent trend in injury rates was observed over the period of the study.

Adolescent

Sensory and motor integration during mandibular function.

The subject of pain is intimately related to that of mandibular function. It is now clear that certain types of temporomandibular disorders, particularly myofascial pain dysfunction, result, in part, from rhythmic muscle activity produced by parafunctional oral habits such as diurnal or nocturnal bruxism. Furthermore, in addition to phasic hyperactivity, evidence also suggests that masticatory muscles of patients with MPD are tonically hyperactive. The pain associated with such hyperactive musculature prompts many patients to seek professional help. This article provides an updated historical review of one important aspect of mandibular function and gives insight into the general "state of the art."

Animals

Global visual processing in the monkey superior colliculus.

Neurons were recorded in the superficial layers of the superior colliculus in anesthetized monkeys. As classically described, cells were non-selective for target direction and speed when the target moved through an empty visual field. However, these same cells were sensitive to target direction and speed relative to a textured moving background. The target's response was suppressed when its direction and speed were similar to that of the background, irrespective of the absolute direction of background movement.

Animals

Simultaneous assessment of segmental and global left ventricular function by two-dimensional echocardiography in acute myocardial infarction.

Both segmental and global left ventricular performance were assessed simultaneously in 29 patients with acute myocardial infarction using two-dimensional echocardiography. Comparisons were made between left ventricular wall motion versus peak CK-MB, site of infarction, and occurrence of heart failure. Two-dimensional echocardiography identified areas of dyssynergy which corresponded to electrocardiographic areas of infarction in 89% of all cases. Patients with heart failure had more dyssynergic segments, and these segments manifested more severe dyssynergy than patients without heart failure. Patients with severe global dysfunction manifested higher peak CK-MB values, and those with anterior infarction had more global dyssynergy than did those patients with inferior infarction. These observations suggest that two-dimensional echocardiography is a useful technique for localization and assessment of segmental and global dyssynergy in acute myocardial infarction. Information so derived correlates with the clinical status of patients with acute myocardial infarction, and may offer important insights into both prognosis and treatment.

Creatine Kinase

Cutaneous sensory thresholds from skin overlying masseter and forearm in MPD patients and controls.

Cutaneous sensory thresholds from skin overlying both masseters and right ventral forearm were measured in a group of 12 MPD patients and an appropriately matched group of non-patients. No significant differences were found between the two groups, nor were there significant differences between symptomatic and contralateral asymptomatic sites in the patients. There does not appear to be evidence for differences in sensory characteristics in the cutaneous afferent pathway of MPD patients.

Adolescent