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Biomedical subjects

David A Wilson

Publications and source records attributed to David A Wilson.

6 recordsLinked to original sources

Using the amide proton signals of intracellular proteins and peptides to detect pH effects in MRI.

In the past decade, it has become possible to use the nuclear (proton, 1H) signal of the hydrogen atoms in water for noninvasive assessment of functional and physiological parameters with magnetic resonance imaging (MRI). Here we show that it is possible to produce pH-sensitive MRI contrast by exploiting the exchange between the hydrogen atoms of water and the amide hydrogen atoms of endogenous mobile cellular proteins and peptides. Although amide proton concentrations are in the millimolar range, we achieved a detection sensitivity of several percent on the water signal (molar concentration). The pH dependence of the signal was calibrated in situ, using phosphorus spectroscopy to determine pH, and proton exchange spectroscopy to measure the amide proton transfer rate. To show the potential of amide proton transfer (APT) contrast for detecting acute stroke, pH effects were noninvasively imaged in ischemic rat brain. This observation opens the possibility of using intrinsic pH contrast, as well as protein- and/or peptide-content contrast, as diagnostic tools in clinical imaging.

Animals↗

Bronchodilator premedication does not decrease respiratory adverse events in pediatric general anesthesia.

PURPOSE: Upper respiratory infections (URI) presage perioperative respiratory complications, but thresholds to cancel surgery vary widely. We hypothesized that autonomically-mediated complications seen during emergence from anesthesia would be predicted by capnometry and reduced with preoperative bronchodilator administration. METHODS: Afebrile outpatient tertiary-care children (age two months to 18 yr, n = 109) without lung disease or findings, having non-cavitary, non-airway surgery for under three hours, were randomized to bronchodilator premedication vs placebo and had preoperative capnometry. After halothane via mask, laryngeal mask airway, or endotracheal tube, and regional anesthesia as appropriate, patients recovered breathing room air while cough, wheeze, stridor, laryngospasm, and cumulative desaturations were recorded for 15 min. RESULTS: In this specific population, there was no association between adverse events and either URI within six weeks (n = 76) or URI within seven days (n = 21). Neither albuterol nor ipratropium premedication decreased adverse events. Endotracheal intubation was associated with increased emergence desaturations and placebo nebulized saline increased emergence coughing. Neither anesthesiologists nor preoperative capnometry predicted adverse events. CONCLUSIONS: Adverse events were neither predicted nor prevented. In afebrile outpatient ASA I and II children with no lung disease or findings, having non-cavitary, non-airway surgery for under three hours, there was no association between either recent URI or active URI and desaturation, wheeze, cough, stridor, or laryngospasm causing desaturation (all P > 0.05). In this highly selected population of afebrile patients, the results suggest that anesthesiologists may proceed with surgery using specific criteria in the presence of a URI.

Anesthesia, General↗

Treatment of transtentorial herniation unresponsive to hyperventilation using hypertonic saline in dogs: effect on cerebral blood flow and metabolism.

We tested the hypothesis that transtentorial herniation (TTH) represents a state of cerebral ischemia that can be reversed by hypertonic saline. Because of the high mortality associated with TTH, new therapeutic strategies need to be developed for rapid and effective reversal of this process. We produced TTH (defined by acute dilatation of one or both pupils) by creating supratentorial intracerebral hemorrhage with autologous blood injection in seven mongrel dogs anesthetized using intravenous pentobarbital and fentanyl. We measured serial rCBF (regional cerebral blood flow) using radiolabeled microspheres in regions around and distant to the hematoma. Cerebral oxygen extraction and oxygen consumption (CMRO2) were measured by serial sampling of cerebral venous blood from the sagittal sinus. Mean arterial pressure (MAP) and intracranial pressure (ICP) were continuously monitored. TTH was successfully reversed over a mean period of 25.7 +/- 4.9 minutes after intravenous administration of 23.4% sodium chloride (1.4 mL/kg) in all animals. All measurements were recorded 15, 30, 60, and 90 minutes after administration of 23.4% sodium chloride. Compared to prehematoma ICP (14.1 +/- 1.7 mm Hg, mean +/- SE), elevation in ICP was observed during TTH (36.2 +/- 7.2 mm Hg) with no change in cerebral perfusion pressure (CPP) (80.4 +/- 4.7 vs. 76.7 +/- 10.1 mm Hg) because of concomitant elevation in mean arterial pressure. Compared to baseline values, there was a reduction in rCBF (mL/100 gm/min +/- SE) in brainstem (12.1 +/- 2.0 vs. 21.4 +/- 1.4), gray matter (18.2 +/- 2.1 vs. 31.4 +/- 1.8), and white matter (8.6 +/- 1.7 vs.18.7 +/- 0.9) in the hemisphere contralateral to the hematoma; and gray matter (12.9 +/- 2.9 vs. 27.9 +/- 2.2) and white matter (8.3 +/- 2.0 vs.19.9 +/- 1.0) in the ipsilateral hemisphere distant from the hematoma. Administration of 23.4% sodium chloride resulted in reduced ICP at 15 minutes (12.7 +/- 1.4) and 30 minutes (15.6 +/- 3.1) after administration. RCBF values were restored in all regions studied after administration of 23.4% sodium chloride with an increase in CMRO2 (1.8 +/- 0.4 vs. 3.9 +/- 0.7 mL O2 /100 gm/min). Compared with baseline values, rCBF increased in the ipsilateral (31.7 +/- 2.5 vs. 63.4 +/- 11.7) and contralateral (28.7 +/- 1.9 vs. 45.5 +/- 5.7) thalamus at 15 minutes after administration of 23.4% sodium chloride. TTH represented a state of ischemia in brainstem and supratentorial gray and white matter in the presence of adequate CPP, suggesting mechanical compression of vessels at the level of tentorium. Hypertonic saline reversed TTH, and restored both rCBF and CMRO2, although hyperemia was observed immediately after reversal of TTH. Administration of hypertonic saline may preserve neurologic function during the interim period between TTH and surgical intervention.

Animals↗

Paranasal meningioma in a horse.

Paranasal meningioma was diagnosed in a 5-year-old Appaloosa gelding. The mass occupied the right maxillary, frontal, and sphenopalatine sinuses but did not invade the calvarium. The diagnosis was based on histologic evaluation, positive immunohistochemical staining for vimentin and cytokeratin, and ultrastructural features including the presence of interdigitating spindle cells with numerous desmosomes.

Animals↗

Factors regulating collagen synthesis and degradation during second-intention healing of wounds in the thoracic region and the distal aspect of the forelimb of horses.

OBJECTIVE: To determine significant molecular and cellular factors responsible for differences in second-intention healing in thoracic and metacarpal wounds of horses. ANIMALS: 6 adult mixed-breed horses. PROCEDURE: A full-thickness skin wound on the metacarpus and another such wound on the pectoral region were created, photographed, and measured, and tissue was harvested from these sites weekly for 4 weeks. Gene expression of type-I collagen, transforming growth factor (TGF)-beta1, matrix metalloproteinase (MMP)-1, and tissue inhibitor of metalloproteinase (TIMP)-1 were determined by quantitative in situ hybridization. Myofibroblasts were detected by immunohistochemical labeling with alpha-smooth muscle actin (alpha-SMA). Collagen accumulation was detected by use of picrosirius red staining. Tissue morphology was examined by use of H&E staining. RESULTS: Unlike thoracic wounds, forelimb wounds enlarged during the first 2 weeks. Myofibroblasts, detected by week 1, remained abundant with superior organization in thoracic wounds. Type-I collagen mRNA accumulated progressively in both wounds. More type-I collagen and TGF-beta1 mRNA were seen in forelimb wounds. Volume of MMP-1 mRNA decreased from day 0 in both wounds. By week 3, TIMP-1 mRNA concentration was greater in thoracic wounds. CONCLUSIONS AND CLINICAL RELEVANCE: Greater collagen synthesis in metacarpal than thoracic wounds was documented by increased concentrations of myofibroblasts, type-I collagen mRNA,TGF-beta1 mRNA, and decreased collagen degradation (ie, MMP-1). Imbalanced collagen synthesis and degradation likely correlate with development of exuberant granulation tissue, delaying healing in wounds of the distal portions of the limbs. Factors that inhibit collagen synthesis or stimulate collagenase may provide treatment options for horses with exuberant granulation tissue.

Animals↗

Accelerometer-based system for the detection of lameness in horses.

Video-based kinematic analysis of gait in horses is accurate for quantification of lameness and reliable for identification of the affected limb. Algorithms for the measurement of the vertical head and pelvic displacement and phase correlation with vertical displacement of one forelimb and hindlimb foot have been developed for this purpose. However, because of camera field-of-view limitations, video-based analysis of gait can only be reliably accomplished with the horse constrained to move on a treadmill. This paper describes the use of 2 single-axis accelerometers and 2 gyroscopic transducers as a measurement system for the identification and quantification of forelimb and hindlimb lameness in horses. Vertical head and pelvic acceleration are converted to displacement, lameness is quantified from previously developed algorithms, and affected limb is determined by correlation of head and pelvic signals with gyroscopic signals from the right forelimb and hindlimb feet. Signals from the 4 transducers are telemeterized at 200 Hz and collected to a receiver connected to a lap top computer, freeing the horse from the constraints of a treadmill laboratory setting. In this paper we describe the reliability of this new accelerometer-based system in horses with induced lameness while trotting on a treadmill and freely outside overground.

Animals↗