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Biomedical subjects

D L Clark

Publications and source records attributed to D L Clark.

At least 55 records · Page 3Linked to original sources

Halothane metabolism in acyanotic and cyanotic patients undergoing open heart surgery.

The metabolism of halothane was examined in patients with acyanotic and cyanotic congenital heart disease undergoing open heart surgery. Statistically significant (P less than 0.05) pre-surgical differences between acyanotic and cyanotic groups included pH (7.46 +/- 0.02 vs 7.36 +/- 0.02), PaO2 (277 +/- 58 vs 51 +/- 3 torr), O2 saturation (97 +/- 1 vs 74 +/- 4%), and hematocrit (45 +/- 3 vs 58 +/- 2%). Serum fluoride levels were significantly greater in cyanotic than in acyanotic groups 2-4 hours after initial exposure to halothane. Both groups had significant intragroup increases in serum levels of fluoride, bromide, and trifluoroacetic acid. Significant increases in serum levels of lactate dehydrogenase, creatinine phosphokinase, and glutamic oxaloacetate transaminase were observed in both groups, whereas, the cyanotic patients had additional significant increases in blood urea nitrogen and direct bilirubin. The cyanotic group also had higher total and direct serum bilirubin levels than the acyanotic group. Therefore, patients with cyanotic congenital heart disease had greater reductive metabolism of halothane than acyanotics. However, cyanotic and acyanotic patients had essentially similar postoperative derangements in hepatic and renal function.

Cardiopulmonary Bypass↗

Effects of diabetes mellitus on renal fatty acid activation and desaturation.

We report the first direct measurement of delta-6 desaturase and delta-9 desaturase (EC 1.3.99.3, acyl-CoA dehydrogenase) activities in the rat kidney. Crude renal cortical homogenates from alloxan-diabetic and from normal rats were assayed for delta-6 and delta-9 desaturase activities. The delta-6 desaturation pathway activity measured with 9,12-octadecadienoic acid (linoleic acid) as substrate was increased, while the delta-9 desaturation pathway measured with hexadecanoic acid (palmitic acid) as substrate was unchanged in diabetic renal cortex, suggesting that the two enzymes are regulated independently in this tissue. In contrast to the kidney, delta-6 desaturase pathway activity was unchanged and the delta-9 desaturase pathway activity was greatly depressed in diabetic liver. When exogenous long-chain acyl-CoA synthetase (EC 6.2.1.3; acid: CoA ligase, AMP-forming) was added to the delta-6 desaturase assay system, the rate of delta-6 desaturation in normal kidney increased to a rate similar to that found in diabetic kidney; rates in diabetic extracts were unchanged. These results suggest that the rate of fatty acid substrate activation to the coenzyme A ester limits the rate of delta-6 desaturation in normal renal cortex. These results also suggest that the rate of fatty acid activation by long-chain acyl-CoA synthetase activity is increased in diabetic renal cortex. Direct measurement of the activity of long-chain acyl-CoA synthetase demonstrated that its activity was indeed increased significantly in the renal cortex of diabetic rats.

Acyl-CoA Dehydrogenase, Long-Chain↗

Leimyosarcoma of the urinary bladder. 13 years after cyclophosphamide therapy for Hodgkin's disease.

A leiomyosarcoma of the urinary bladder occurred in a 17-year-old boy who was treated with a total dose of 67 g cyclophosphamide over a period of 5 years for Hodgkin's disease diagnosed at the age of 4. Cyclophosphamide was discontinued at the age of 9 because of gross hematuria, and intermittent hematuria recurred 8 years after (at the age of 17) the cessation of this drug. A large exophytic tumor found in the urinary bladder was diagnosed as leiomyosarcoma by light and electron microscopic studies. In addition, there were microscopic features of long-term cyclophosphamide toxicity throughout the bladder wall.

Adult↗

Effect of hypothermic cardiopulmonary bypass on nitroprusside metabolism.

At a rectal temperature of 25 degrees C, six patients undergoing hypothermic cardiopulmonary bypass received intravenous infusions of sodium nitroprusside (SNP) at a rate of 7.3 +/- 1.7 micrograms/kg/min for 20 minutes. Total SNP dose per patient was 11.0 +/- 1.1 mg. Blood samples for serum cyanide (CN-), red blood cell cyanide (RBC CN-), and thiocyanate (SCN-) determinations were drawn immediately before SNP infusion. These determinations were repeated at the end of the infusion, at the start of rewarming, and at a rectal temperature greater than 34 degrees C and 1, 4 (five subjects), and 24 hours (three subjects) thereafter. Extracorporeal blood flow was held constant at 2.4 L/min/m2 and mean arterial pressure was maintained between 50 to 100 mm Hg with phenylephrine (3.62 +/- 0.75 mg) during SNP infusion and trimethaphan (37.8 +/- 15.6 mg) after the end of the infusion. There was a significant increase in RBC CN- after the SNP infusion that lasted until the subjects were rewarmed. One subject developed a peak RBC CN- level of 0.8 microgram/ml. Plasma CN- levels changed little throughout and SCN- levels were elevated only after rewarming. The nonenzymatic release of free CN- from SNP was not inhibited by hypothermia, while the enzymatic detoxification of CN- to SCN- may have been delayed.

Aged↗

Hemodynamic and anesthetic effects of sufentanil as the sole anesthetic for pediatric cardiovascular surgery.

The efficacy, safety, and hemodynamic response to 5 micrograms/kg, 10 micrograms/kg, or 20 micrograms/kg of sufentanil and 0.1 mg/kg pancuronium was evaluated in children between 4 and 12 years of age scheduled for open heart surgery. Systolic time intervals, 2-D echocardiograms, systolic blood pressures (SBP), diastolic blood pressures (DBP), and heart rates (HR) were recorded before and after induction of anesthesia. Significant changes 10 min following induction of anesthesia but before intubation included increases in SBP in the 5 micrograms/kg group (P less than 0.01) and in the ratio of preejection period to left ventricular ejection time in the 20 micrograms/kg group (P less than 0.05). Instances of myoclonic jerking and coughing episodes were observed in all three study groups. Following intubation there were significant (P less than 0.05) increases in SBP in all groups, in DBP in the 5 micrograms/kg group, and in HR in the 5 micrograms/kg and 10 micrograms/kg groups. Smaller increases in SBP, DBP, and HR were seen in all groups after skin incision and sternotomy. Mean plasma catecholamine levels showed nonsignificant increases following periods of intraoperative stimulation with wide patient variations. Recovery of responsiveness to command occurred in all groups within one hour from the end of surgery but extubation was impeded by shallow periodic breathing and hypercapnea. The authors conclude that for children undergoing open heart surgery use of sufentanil as a sole anesthetic in bolus form did not provide a reliable depth of anesthesia with any of the induction doses studied.

Anesthesia, Intravenous↗

Effects of advanced age on extravascular lung water accumulation during coronary artery bypass surgery.

Pulmonary extravascular thermal volume (ETVL) accumulation during aortocoronary bypass grafting (CABG) was compared between nine patients (group 1) aged 49 +/- 2 (SEM) yr and nine patients (group 2) aged 65 +/- 1.2 yr, using the thermal-dye technique. Before extracorporeal bypass (ECB), ETVL was significantly correlated with age and mean ETVL was significantly lower in group 1 (3.93 +/- 0.48 ml/kg body weight) than group 2 (5.93 +/- 0.38 ml/kg). During ECB, ETVL rose to 5.15 +/- 0.65 ml/kg in group 1 (p less than .05) and to 6.38 +/- 0.56 ml/kg in group 2. By the next morning, ETVL had returned to pre-ECB levels. Post-ECB, cardiac index decreased in group 1 and colloid osmotic pressure decreased in both groups, but all values returned to pre-ECB levels by the next morning. Although PaO2 had decreased and pulmonary shunt fraction had increased by this time, changes in these variables did not correlate with changes in ETVL. During ECB, ETVL increased transiently but returned to pre-ECB levels by the next morning.

Aged↗

Vestibular and visual rotational stimulation as treatment for attention deficit and hyperactivity.

Previously published studies report an improvement in hyperactivity following exposure to vestibular semicircular canal stimulation under eyes-open, lights-on conditions (conditions that provide visual feedback). To separate the effectiveness of vestibular stimulation from that of visual stimulation, 30 primary school children who met the criteria for having attention deficit disorder with hyperactivity were enrolled in a split-sample Latin square crossover study. The effects of just vestibular stimulation and of just visual stimulation were compared with the effect of combined vestibular and visual stimulation. Behavior ratings showed significant improvement at the end of the last treatment and at follow-up one year later; this is not easily explained by statistical regression, history, or the placebo effect. The most improvement was with solitary vestibular stimulation, which showed large effect sizes; however, differences from the other two conditions failed to reach significance at traditional p levels.

Acoustic Stimulation↗

Effects of colloid or crystalloid administration on pulmonary extravascular water in the postoperative period after coronary artery bypass grafting.

The effect of postoperative fluid management on pulmonary extravascular thermal volume (ETVL) as in index of pulmonary extravascular water after coronary artery bypass grafting was compared, using the thermal-dye technique, among five patients who received 5% albumin (group A), five patients who received 6% hydroxyethyl starch (group H), and five who received lactated Ringer's solution (group C). Intraoperatively, all patients received lactated Ringer's solution intravenously, and the cardiopulmonary bypass (CPB) circuit prime included 5% albumin. No statistically significant changes in ETVL occurred postoperatively in any group, nor did ETVL differ significantly between groups. After CPB, colloid osmotic pressure (COP) significantly decreased and pulmonary artery wedge pressure (WP) and the WP-COP gradient significantly increased in each group, implying an increase in transcapillary fluid flux. Cardiac index changed variably. Pulmonary shunt fraction (Qsp/Qt) did not change in groups A and C but decreased during CPB in group H (from 0.22 +/- 0.03 to 0.16 +/- 0.11). Postoperatively, patients in the three groups received similar volumes of fluids and had similar perioperative weight gains. By the next morning (AM1), COP increased in all groups, returning to levels noted before CPB in group C, and exceeding these levels in groups A and H. Wedge pressure was similar in all three groups on AM1. PaO2 decreased significantly, and alveolar-arterial oxygen partial pressure difference increased significantly in all groups on AM1. In Group H, Qsp/Qt returned to levels observed before CPB by AM1 (0.27 +/- 0.09). We conclude that in patients without postoperative increases in WP, ETVL changes minimally during CPB and is not influenced by the type of fluid administered as the primary volume replacement in the postoperative period.

Aged↗

The effect of ventilation on systemic blood gases in the presence of left ventricular ejection during cardiopulmonary bypass.

The effect of pulmonary ventilation upon systemic arterial blood gases during cardiopulmonary bypass in the presence of left ventricular ejection was evaluated in 20 adult male patients undergoing coronary artery bypass grafting. Following rewarming, establishment of a sinus rhythm, and production of a pulse pressure of at least 20 mm Hg on the arterial pressure trace caused by left ventricular ejection, arterial blood gases were obtained from the arterial and venous extracorporeal circuits and the radial arterial cannula. Patients were then randomly assigned to a nonventilation (n = 10) or a ventilation (n = 10) group. The ventilation group was given 10 breaths/min with 100% oxygen at a tidal volume of 10 ml/kg. Whereas the nonventilation group received apneic oxygenation at zero end-expiratory pressure. After 5 minutes the arterial blood gas data were again obtained. Significant findings (p less than 0.05) included decreases in systemic carbon dioxide tension and increases in systemic pH in the ventilation group and decreases in systemic oxygen tension in the nonventilation group. Although the changes in the arterial blood gases were significant, these changes occurred well within the limits of clinical acceptability. It is concluded that left ventricular ejection for short periods during full cardiopulmonary bypass does not necessitate pulmonary ventilation.

Aged↗

The effect of hypothermic cardiopulmonary bypass on patients with low-titer, nonspecific cold agglutinins.

The effect of hypothermic cardiopulmonary bypass (CPB) was studied in 5 patients with strongly positive cold agglutination at 4 degrees C (experimental group) and in 10 controls. In the in vitro part of the study, the characteristics of the cold agglutinin antibodies in the experimental group included a low thermal amplitude (28 degrees C or less), a low 4 degrees C agglutination titer (1:32 or less), and nonspecificity (non-anti-I and non-anti-i). The in vivo portion of the study revealed a fall in total urine and serum free hemoglobin in both groups on going on bypass, followed by a rise for the remainder of bypass. Statistical comparison between observed and expected total free hemoglobin for both groups showed a significant rise (p less than 0.05) after bypass, thereby indicating ongoing hemolysis. No statistically significant difference between preoperative and post-operative blood urea nitrogen and creatinine levels and gross neurological status was observed in the experimental group. It was concluded that the patient with nonspecific cold agglutinins whose antibody is characterized by a low titer, a low thermal amplitude, and a lack of clinical symptomatology can undergo hypothermic CPB without increased threat of a hemolytic or vascular occlusive crisis.

Aged↗

Emergency guide wire pacing: new methods for rapid conversion of a cardiac catheter into a pacemaker.

We developed a new electrode to convert rapidly a previously inserted pulmonary artery or left ventricular catheter into a pacemaker. One method of doing this is by withdrawal of the pulmonary artery catheter from the pulmonary artery to the right ventricle by pressure control, and a Teflon-coated guide wire, stripped of 5 mm of insulation at its tip, is advanced through the catheter to contact the endocardium. In the second method, the pacing electrode is advanced through the distal lumen of the catheter while it is positioned within the pulmonary artery and withdrawn into the right ventricle while pacing. Finally, a third method involves advancement of the guide wire electrode into the left ventricle through a pigtail catheter. To pace, the guide wire electrode is connected to the cathode of a pacemaker referenced to a skin electrode. We paced 10 of 10 right heart cardiac catheterization, intra- and postoperative surgery patients by methods 1 and 2, and 4 of 4 left heart catheterization patients by method 3. Thresholds (mean +/- SEM) for guide wire pacing were: right ventricle 1.52 +/- 0.4 mA; left ventricle 1.33 +/- 0.1 mA. Guide wire pacing is rapid, reliable, and requires little operator skill. Our indications for guide wire pacing are: 1) emergency right ventricular pacing in operative or intensive care unit patients with unexpected bradyarrhythmias who have an indwelling pulmonary artery catheter; and 2) emergency left ventricular pacing in left heart cardiac catheterization patients with contrast-induced bradyarrhythmias.

Bradycardia↗

Hemodynamic effects of calcium chloride in adults with regurgitant valve lesions.

We evaluated the hemodynamic effects of 7 mg/kg intravenous calcium chloride (CaCl2) or placebo in 20 adults with regurgitant aortic and/or mitral valves before and after induction of anesthesia with fentanyl (50 micrograms/kg), followed by pancuronium (0.1 mg/kg) and 100% oxygen. CaCl2 produced no changes in mean systemic, pulmonary arterial, central venous, or pulmonary capillary wedge pressures or vascular resistances before or after induction of anesthesia. A significant increase in left ventricular stroke work index was seen 1 min after CaCl2 was administered after induction of anesthesia (from 31.29 +/- 3.00 to 37.44 +/- 3.81 g X m X M-2). Before induction, CaCl2 decreased heart rate from 93.9 +/- 9.6 to 85.2 +/- 8.7 beats/min (statistically significant 2.5 and 10 min after CaCl2) and after induction from 104.6 +/- 8.4 to 89.3 +/- 7.5 (significant at 1, 2.5, 5, and 10 min). These results suggest that CaCl2 is associated with an immediate increase in ventricular performance and that the subsequent decrease in heart rate is not sufficient to contraindicate use of CaCl2 as an inotrope in patients with chronic valvular regurgitation. The effects of CaCl2 injection in man on pulmonary shunt fraction (Qs/Qt) have not been described previously. We found no change in Qs/Qt, suggesting that CaCl2 has no direct effect on distribution of pulmonary blood flow.

Aortic Valve Insufficiency↗

Changes in renal phospholipid fatty acids in diabetes mellitus: correlation with changes in adenylate cyclase activity.

Male Sprague-Dawley rats made diabetic with alloxan (37.5 mg/kg) or streptozotocin (65 mg/kg) were killed after 3-6 weeks of disease; renal tissues were studied for phospholipid content and for fatty acid composition of the phospholipids. No consistent change was noted in total phospholipid content nor in the proportion of various phospholipids in diabetics. However, diabetic animals showed a consistent reduction of arachidonic acid content in phosphatidylcholine (PC) and phosphatidylethanolamine in whole renal cortex, plasma membranes purified from renal cortex, and in isolated glomeruli. Associated with the fall in arachidonic acid was a rise in linoleic acid in the samples studied. Insulin therapy returned the fatty acid profiles to normal. These results are similar to patterns observed in other diabetic tissues and suggest that diabetes is associated with generalized changes in cell membranes. That these structural changes may have functional significance is suggested by demonstrated alterations in the temperature-dependence of adenylate cyclase in renal plasma membranes of diabetic animals. Adenylate cyclase is thought to be intimately associated with PC in plasma membranes, a phospholipid showing significant changes in fatty acid content in diabetes (unsaturation index 165 +/- 2 for normals, 147 +/- 5 for diabetics). Na+,K+-ATPase which is thought to be primarily associated in vivo with phosphatidylinositol (PI), shows no change in apparent energy of activation in diabetes. The fatty acid content of PI is minimally altered in diabetes, and the unsaturation index is unchanged.

Adenylyl Cyclases↗

Postrotatory nystagmus in the full-term and premature infant.

Postrotatory nystagmus (PR-N) is an easily elicited reflex reported to be abnormal in developmentally delayed children. PR-N has been recorded in newborns, but methodological difficulties have compromised its full understanding. Eight healthy adults were compared with 15 full-term and 12 premature infants, all neurologically normal, who were tested serially during the first year of life. All subjects were positioned in a rotational chair, spun for 1 min at a constant angular velocity (150 degrees/s) and then abruptly stopped. Primary and secondary PR-N was electronically recorded. Results for full-terms and prematures were similar in all variables, but the number and frequency of beats in both primary and secondary PR-N were significantly greater in adults. Angular displacement and velocity of each beat was significantly higher in infants of all ages. All components of PR-N, whether primary or secondary, can be identified in infants under 1 year of age and are clearly different from those observed in adults. These differences may reflect anatomical and neurophysiological immaturity of eye movement control in the infant.

Adolescent↗

Effects of vestibular stimulation in seizure-prone children. An EEG study.

Concern that vestibular stimulation may induce seizures in seizure-prone children has been based on hearsay and unconfirmed clinical impressions of practicing therapists. To clarify this issue, we took electroencephalographic recordings of seizure-prone children before, during, and after specific vestibular stimulation. Ten children with seizure histories, 5, to 15 years of age, were exposed to warm and cold caloric vestibular stimuli. Electroencephalographic activity was recorded before, during, and after each vestibular stimulus; recordings were rated and compared prevestibular and postvestibular stimulation. Electronystagmographic recordings were also taken. Results show that vestibular stimulation does not accentuate the abnormal brain wave pattern in seizure-prone children. Six of 10 subjects had a significant reduction in paroxysmal activity (p less than .02). Possible explanations for clinical reports of vestibular induced seizures are given, with suggestions for precautions when applying vestibular stimulation to seizure-prone children.

Adolescent↗