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Biomedical subjects

D A Davis

Publications and source records attributed to D A Davis.

At least 73 records · Page 4Linked to original sources

Hypothermia enhances contractility in cerebral arteries of newborn lambs.

Hypothermia is the major factor influencing autoregulatory properties of the cerebral circulation in human infants undergoing hypothermic cardiopulmonary bypass. The present investigation evaluated the effect of decreased temperature on the contractility of isolated middle cerebral arteries obtained from newborn lambs. Reducing bath temperature from 37 to 21 degrees C caused a temperature-dependent increase in contractile tension, achieving 1.32 +/- 0.09 g above resting tension (0.75 g). Pretreatment with nonselective (alpha 1 and alpha 2) alpha-adrenoceptor antagonist, phentolamine (10(-5) M), with an inhibitor of nitric oxide synthase, NG-nitro-L-arginine methyl ester hydrochloride (10(-4) M), and with a cyclooxygenase inhibitor, indomethacin (10(-5) M), did not affect the contractile response to a decrease in bath temperature from 37 to 21 degrees C. Furthermore, cerebral arteries were responsive to both norepinephrine (constriction) and sodium nitroprusside (relaxation) and the sensitivity of cerebral arteries to the sympathetic neurotransmitter norepinephrine appears to be enhanced at low temperatures. We postulate that direct cerebral vasoconstriction and enhanced adrenergic contractility may be responsible for increased cerebrovascular resistance during and after hypothermic cardiopulmonary bypass with possible ischemic cerebral injury and neurological sequelae.

Animals↗

Dose-dependent differences in the development of reserpine-induced oral dyskinesia in rats: support for a model of tardive dyskinesia.

Rats treated with reserpine develop spontaneous orofacial dyskinesia that has features similar to tardive dyskinesia (TD) in humans. In contrast to TD, however, reserpine-induced oral dyskinesia develops rapidly reaching a maximal level within 3 days at a dose of 1 mg/kg per day. The present study examined whether rats administered lower doses of reserpine would develop the oral dyskinesia at a slower rate, similar to the protracted development of TD. Rats were administered 0, 0.01, 0.05, 0.1, or 1.0 mg/kg reserpine subcutaneously every other day for 100 days. Oral dyskinesia was measured by recording the incidence of tongue protrusions for 30 min on days 1, 4, 10, 20, 40, 60, and 100. The time course of the development of reserpine-induced oral dyskinesia varied dose-dependently. The response was evident within 4 days at 1 mg/kg, within 20 days at 0.1 mg/kg, within 60 days at 0.05 mg/kg, and was not evident at 0.01 mg/kg at any time during the 100 days of treatment. The protracted development of reserpine-induced oral dyskinesia at the lower doses is consistent with TD. Doses of reserpine that produced an increase in tongue protrusions also produced a 90-95% depletion of dopamine and an increase in the ratio of dopamine metabolites to dopamine in the caudate-putamen. The disruption of dopamine neurotransmission may be involved in development of the oral dyskinesia. Furthermore, it is suggested that the 1 mg/kg dose of reserpine may induce neurochemical changes similar to that produced by long-term neuroleptic treatment, but at an accelerated rate, thereby providing a new efficient model of TD.

Animals↗

High-frequency jet versus conventional ventilation in infants undergoing Blalock-Taussig shunts.

Nine infants undergoing modified Blalock-Taussig shunts were randomized to both high-frequency jet ventilation (HFJV) and conventional ventilation (CV). Vital signs, blood gases, mean airway pressure, lung mechanics, functional residual capacity, and lung movement were compared on both modes of ventilation keeping peak inspiratory and expiratory pressures constant. The mean airway pressure was lower on HFJV than on CV (8.5 versus 10.9 cm H2O). Arterial partial pressure of oxygen was greater on HFJV than on CV (55 versus 46 mm Hg), arterial partial pressure of carbon dioxide was lower on HFJV than on CV (28 versus 37 mm Hg), whereas compliance (0.54 versus 0.56 mL.cm H2O-1.kg-1). resistance (110 versus 95 cm H2O/L.s), and functional residual capacity (23 versus 22.5 mL/kg) remained the same. Lung movement and degree of retraction necessary for surgical exposure as evaluated by an independent observer was less with HFJV compared with CV. Compared with CV during the creation of Blalock-Taussig shunts, HFJV provides better gas exchange at lower mean airway pressure with similar lung function, lung volume, and hemodynamics.

Airway Resistance↗

Cutaneous stigmata of occult spinal dysraphism.

We describe a 4-year-old Hispanic boy with a dermal pit and an overlying macular vascular malformation in the lumbosacral area. Magnetic resonance imaging of the region revealed an intraspinal lesion at L1-L2. A fibrous tract was excised. A benign lipoma intrinsic to the roots of the cauda equina was noted at surgery. The cutaneous stigmata of occult spinal dysraphisms are reviewed.

Child, Preschool↗

Competency assessment of primary care physicians as part of a peer review program.

OBJECTIVE: To design and test a program that assesses clinical competence as a second stage in a peer review process and to determine the program's reliability. DESIGN AND SETTING: A three-cohort study of Ontario primary care physicians. PARTICIPANTS: Reference physicians (n = 26) randomly drawn from the Hamilton, Ontario, area; volunteer, self-referred physicians (n = 20); and physicians referred by the licensing body (n = 37) as a result of a disciplinary hearing or peer review. MAIN OUTCOME MEASURES: Standardized patients, structured oral examinations, chart-stimulated recall, objective structured clinical examination, and multiple-choice examination. RESULTS: Test reliability was high, ranging from 0.73 to 0.91, and all tests discriminated among subgroups. Demographic variables relating to the final category were age, Canadian or foreign graduates, and whether or not participants were certified in family medicine. CONCLUSIONS: The study demonstrated the feasibility, reliability, and validity of a multicomponent examination in the peer review process.

Adult↗

DMBA induces programmed cell death (apoptosis) in the A20.1 murine B cell lymphoma.

The mechanism by which 7,12-dimethylbenz[a]anthracene (DMBA) produces cytotoxicity in lymphocytes was investigated in these studies using the murine A20.1 B cell lymphoma. Results show that in vitro exposure of these cells to 10-30 microM DMBA for 4 hr produced an increase in intracellular Ca2+, DNA fragmentation, and subsequent cell death. Elevation of Ca2+ and DNA fragmentation induced by DMBA were greatly pronounced when the A20.1 cells were exposed at high cell density (10(7) cells/ml). DMBA-induced DNA fragmentation and cell death were inhibited by coexposure of A20.1 cells to a calcium chelator (EDTA), a general nuclease and polymerase inhibitor (aurintricarboxylic acid), and a protein synthesis inhibitor (cycloheximide). These agents have been previously shown to inhibit apoptosis in lymphocytes and other cells exposed to chemical agents. We also found that cyclosporin A, an inhibitor of Ca(2+)-dependent pathways of T and B cell activation, prevented apoptosis in the A20.1 cell line. These results demonstrate that DMBA induces programmed cell death (apoptosis) in the A20.1 murine B cell lymphoma by Ca(2+)-dependent pathways. The increased sensitivity of A20.1 at high cell density to Ca2+ elevation and DNA fragmentation suggests that cell to cell interactions may also be important in this process.

9,10-Dimethyl-1,2-benzanthracene↗

Operative creation of left to right cardiac shunts: pulmonary functional sequelae.

The creation of left to right cardiac shunts in neonates is frequently complicated by pulmonary morbidity in the immediate postoperative course. To elucidate the pattern, severity, and cause of lung dysfunction, pulmonary function testing was performed preoperatively and 1, 3, and 7 days postoperatively on 7 neonates undergoing Blalock-Taussig shunting. Pulmonary mechanics (compliance, conductance) were determined with esophageal manometry and pneumotachography, and functional residual capacity was measured by the helium dilution technique. The infants had pulmonary function preoperatively that was similar to that of healthy term neonatal controls. Significant decreases in compliance, conductance, and functional residual capacity were found on the first postoperative day (57%, 21%, and 53% of predicted, respectively). Alterations in conductance were more severe than those in compliance, but both were low through postoperative day 3. Functional residual capacity was the least affected parameter and recovered by postoperative day 3. All parameters were normal by postoperative day 7. These data indicate that shunting is associated with pulmonary morbidity through the third postoperative day that affects the airways more than the lung parenchyma. Pulmonary function studies of these infants may clarify the etiology of pulmonary dysfunction and have an impact on therapeutic strategies used in neonates undergoing cardiac operations.

Heart Defects, Congenital↗

Staged repair of pentalogy of Cantrell with tetralogy of Fallot.

We report a successful two-stage repair of tetralogy of Fallot associated with pentalogy of Cantrell. The first stage, performed in the neonatal period, consisted of repairing the omphalocele, separating the peritoneal from the pericardial cavities, and covering the heart. The second stage, performed at 6 years of age, consisted of complete intracardiac repair and placing the heart in the chest. The patient is alive and well 18 months after the operation.

Abnormalities, Multiple↗

Management of airway obstruction in patients with congenital heart defects.

Airway obstruction may complicate the course of infants undergoing repair of congenital heart disease. Airway obstruction was encountered in seven patients following surgery for complex congenital heart defects (two with interrupted aortic arch, one with pulmonary atresia and a ventricular septal defect, one with tetralogy of Fallot and an abnormal left anterior descending coronary artery, one with truncus arteriosus, and two with complex univentricular heart). In four patients, a conduit was implanted at the time of surgery. In all cases, bronchoscopy accurately demonstrated the cause of the airway obstruction. Two infants had hypoplasia of the left bronchus, and five had tracheobronchomalacia associated with extrinsic compression of the airway by a great vessel or conduit. All were treated conservatively with therapeutic bronchoscopy, tracheotomy, and/or stenting with prolonged mechanical ventilation. Follow-up ranged from 2 to 40 months. Four infants have been weaned from mechanical ventilation and decannulated; two are awaiting decannulation; and one was decannulated and died awaiting surgical repair. To reduce morbidity in infants undergoing surgery for congenital heart disease, the presence of preoperative airway anomalies should be sought and surgery planned to avoid airway compression. Conservative management using diagnostic and therapeutic bronchoscopy, tracheotomy, and stenting together with prolonged ventilator care is rewarding.

Bronchial Diseases↗

Silent cerebral microemboli occurring during carotid angiography: frequency as determined with Doppler sonography.

OBJECTIVE: The purpose of this study was to determine the frequency of occult cerebral embolic events during carotid angiography and the relationship of these events to different phases of the procedure. SUBJECTS AND METHODS: Fifteen patients undergoing carotid angiography were prospectively evaluated by using continuous transcranial Doppler monitoring. Realtime visual and auditory confirmations of emboli were accomplished by recognizing their specific spectral signature and harmonic quality. Specific phases of the examination, such as manipulation of the catheter and guidewire, flushing of the catheter, and injecting contrast material were documented and correlated with embolic occurrences. RESULTS: A total of 1100 embolic phenomena were detected in the middle cerebral artery during carotid angiography. Of these, 944 occurred during catheter flushing and injection of contrast material, and 156 occurred during catheter and wire manipulation. In each patient, more emboli occurred during catheter flushing and injection of contrast material than during manipulation of the catheter and guidewire. No gross neurologic sequelae occurred. CONCLUSION: Embolic phenomena occur frequently during all phases of uncomplicated cerebral angiography.

Aged↗

Detection of microemboli in patients with artificial heart valves using transcranial Doppler: preliminary observations.

Embolic events, particularly involving the central nervous system, represent one of the important hazards associated with the implantation of mechanical valves. The use of the transcranial Doppler to insonate the middle cerebral artery has allowed us to detect microembolic events in some of these patients. Patients with long term implantation and frequent microemboli appear to be more prone to transient ischemic attacks or stroke. Evaluation of 26 patients with mechanical valves revealed 14 with detectable microemboli, four of whom experienced central nervous system symptoms. Modifications in the medical or anticoagulant regimes have not been successful in decreasing or eliminating these microemboli. As the transcranial Doppler is a non-invasive means of quantifying these microemboli, it may become a useful tool in identifying those patients in need of a new type of antithrombotic regimen, or even a valve replacement. Transcranial Doppler could thus provide advance warning before a catastrophic cerebral embolism occurs.

Aortic Valve↗

Evidence for the effectiveness of CME. A review of 50 randomized controlled trials.

OBJECTIVE: To assess the impact of diverse continuing medical education (CME) interventions on physician performance and health care outcomes. DATA SOURCES: Using continuing medical education and related phrases, we performed regular searches of the indexed literature (MEDLINE, Social Science Index, the National Technical Information Service, and Educational Research Information Clearinghouse) from 1975 through 1991. In addition, for these years, we used manual searches, key informants, and requests to authors to locate other indexed articles and the nonindexed literature of adult and continuing professional education. STUDY SELECTION: From the resulting database we selected studies that met the following criteria: randomized controlled trials; educational programs, activities, or other interventions; studies that included 50% or more physicians; follow-up assessments of at least 75% of study subjects; and objective assessments of either physician performance or health care outcomes. DATA EXTRACTION: Studies were reviewed for data related to physician specialty and setting. Continuing medical education interventions were classified by their mode(s) of activity as being predisposing, enabling, or facilitating. Using the statistical tests supplied by the original investigators, physician performance outcomes and patient outcomes were classified as positive, negative, or inconclusive. DATA SYNTHESIS: We located 777 CME studies, of which 50 met all criteria. Thirty-two of these analyzed physician performance; seven evaluated patient outcomes; 11 examined both measures. The majority of the 43 studies of physician performance showed positive results in some important measures of resource utilization, counseling strategies, and preventive medicine. Of the 18 studies of health care outcomes, eight demonstrated positive changes in patients' health care outcomes. CONCLUSION: Broadly defined CME interventions using practice-enabling or reinforcing strategies consistently improve physician performance and, in some instances, health care outcomes.

Clinical Competence↗

Successful treatment of acute postoperative pulmonary hypertension with nifedipine.

We report the successful use of nifedipine in the treatment of acute pulmonary hypertension in an infant after a cardiac operation. This patient had undergone total surgical correction of his truncus arteriosus malformation. He had signs of severe pulmonary artery hypertension unresponsive to hyperventilation, oxygenation, sedation, and a myriad of vasodilators. Nifedipine, 0.2 mg/kg every 4 hours, effectively treated his pulmonary artery hypertension and allowed for a smooth postoperative course and positive outcome.

Humans↗

DMBA-induced cytotoxicity in lymphoid and nonlymphoid organs of B6C3F1 mice: relation of cell death to target cell intracellular calcium and DNA damage.

The purpose of these studies was to evaluate the effects of 7,12-dimethylbenz[a]anthracene (DMBA) on intracellular free Ca2+ and DNA fragmentation in lymphoid cells obtained from the spleen, thymus, and Peyer's patches (PPs) of female B6C3F1 mice. Previous studies in our laboratories have shown that DMBA is cytotoxic to these lymphoid organs and that calcium homeostasis may be impaired following DMBA treatment. The results of the present studies show that a daily oral 14-day exposure of mice to DMBA produced a dose-dependent decrease in the number of viable cells recovered from the spleen, PPs, and thymus. Intracellular levels of Ca2+ were elevated in the spleen and PPs of mice receiving 140 mg/kg of DMBA. Extensive DNA fragmentation was detected in cells obtained from the spleen and PPs, as well as from the thymus. The thymus and PPs demonstrated DNA fragmentation at significantly lower doses of DMBA (42 mg/kg) than did the spleen (140 mg/kg). While cells obtained from the thymus did not demonstrate an elevation in Ca2+ produced by DMBA, in vitro exposure of isolated thymocytes to 3-30 microM DMBA for 4 hr produced significant elevation of intracellular Ca2+. A "ladder-like" pattern of DNA fragmentation was seen by agarose gel electrophoresis of DNA obtained from thymus cells treated with DMBA in vitro, suggesting DNA degradation by endonucleases. Collectively, these studies suggest that DMBA produces lymphotoxicity through an apoptosis-like mechanism involving fragmentation of genomic DNA by Ca(2+)-activated enzymes.

9,10-Dimethyl-1,2-benzanthracene↗