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Biomedical subjects

J C Collins

Publications and source records attributed to J C Collins.

At least 55 records · Page 3Linked to original sources
PubMed1988

The effect of random measurement errors on kinetic transport parameter estimation.

Saturation kinetics experiments, in which uptake U of a substance across a transport barrier is measured as a function of initial concentration difference C, are used to describe transport of nutrients. Many such processes are characterized by low- and high-affinity systems in which kinetic parameters Vmax and Km differ by orders of magnitude. Transformations of equations to straight-line relationships between U and C are popular methods of parameter estimation. The aims of this study are (1) to show effects of random errors in U measurement on Vmax and Km estimation in a two-affinity process under several transformations: Lineweaver-Burk (1/U vs. 1/C), Hanes (C/U vs. C), Eadie-Hofstee (U/C vs. U), and Wolff (U vs. U/C), and (2) to indicate strategies for minimizing effects of errors. Two transport properties will illustrate: an ideal process of low- (Vmax = 100, Km = 10) and high-affinity (Vmax = 1, Km = .1) systems to which random error is added, and experimental uptake of 5-methyltetrahydrofolic acid by isolated hepatocytes.

Age Factors↗
PubMed1987

Effect of allyl alcohol-induced sublethal hepatic damage upon doxorubicin metabolism and toxicity in the rabbit.

A model of hepatic dysfunction in vivo has been developed in rabbits to determine the effects of sublethal hepatocellular necrosis upon doxorubicin pharmacology. Eight New Zealand white rabbits were given 3 mg/kg doxorubicin i.v. Plasma doxorubicin and metabolite pharmacokinetics were determined and toxicity assessed by nadir complete blood counts. Hepatic function was assessed by the pulmonary excretion rate of 14CO2 from [14C]aminopyrine. Hepatocellular necrosis was produced by i.v. injection of 1.35 mg/kg of a 2% allyl alcohol solution. Doxorubicin administration and pharmacokinetics were repeated. Doxorubicin enhances the hepatotoxicity of allyl alcohol. Hepatocellular necrosis does not alter the plasma pharmacokinetics of doxorubicin but does increase the plasma exposure of doxorubicinol. Doxorubicin-induced myelosuppression is enhanced by allyl alcohol pretreatment. These data suggest that in circumstances of reduced hepatocellular volume or acute hepatocellular necrosis, a key plasma marker of doxorubicin-induced acute toxicity may be doxorubicinol.

1-Propanol↗
PubMed1986

The effects of cimetidine upon the plasma pharmacokinetics of doxorubicin in rabbits.

Cimetidine is an H2 antagonist which inhibits cytochrome P-450 and reduces hepatic blood flow. To determine whether cimetidine interferes with the plasma pharmacokinetics of doxorubicin, we gave six female New Zealand rabbits doxorubicin 3 mg/kg, followed a month later by cimetidine 120 mg/kg every 12 h over 72 h and doxorubicin 3 mg/kg. Serial plasma specimens were obtained over 72 h and assayed for doxorubicin and its metabolites by high-performance liquid chromatography and fluorescence detection. Doxorubicin plasma pharmacokinetics were prolonged after cimetidine pretreatment [AUC 0.76 +/- 0.22 vs. 2.85 +/- 1.22 microM X h, no pretreatment vs pretreatment (p = 0.005), half-life = 11.7 +/- 6.55 vs 28.0 +/- 8.16 h (P = 0.0002), and clearance = 0.129 +/- 0.036 vs 0.036 +/- 0.011 l/min-1 kg-1 (P = 0.0007)]. No significant differences were found between the AUCs for doxorubicinol, 7-deoxy doxorubicinol aglycone, or two unidentified nonpolar metabolites in nonpretreatment and pretreatment studies. Cimetidine increases and prolongs the plasma exposure to doxorubicin in rabbits. Doxorubicin metabolism does not appear to be affected by cimetidine.

Animals↗
PubMed1986

Prostacyclin reduction of regional ischemic injury in the canine myocardium.

The effect of prostacyclin (PGI2) on the myocardium of the awake dog subjected to coronary artery occlusion was examined. Animals were randomly administered PGI2 200 ng/kg/min (n = 6), PGI2 100 ng/kg/min (n = 6), or the vehicle control (n = 6), beginning 30 min prior to coronary artery occlusion. Radiolabeled microspheres (15 microns) were used to measure myocardial blood flow. The myocardial region at risk was determined by fluorescein injection, and infarct size was assessed by triphenyl tetrazolium staining. Segmental myocardial function was evaluated from the systolic ejection shortening (SES) by subendocardial ultrasonic dimension crystals in normal, ischemic, and border zones. PGI2 200 ng/kg/min produced significant decreases in aortic pressure and systemic vascular resistance. PGI2 100 ng/kg/min, which achieves 95% platelet inhibition, had no significant hemodynamic effects. Animals receiving PGI2 200 ng/kg/min had significantly higher blood flow to the ischemic region, better border zones SES, and a smaller infarct. PGI2 ameliorates myocardial injury and reduces functional impairment produced by ischemia in doses that elicit vasodilation. This beneficial effect of PGI2 does not appear to be mediated solely by an antiplatelet mechanism.

Animals↗
PubMed1985

Lung vascular transport at controlled pressures with reduced coronary flow in sheep.

This study was performed to measure the effects of sustained coronary flow reduction on lung lymph flow and protein clearance at normal and elevated lung microvascular pressures. Eleven halothane-anesthetized sheep were provided with lung lymph and carotid-to-left-anterior-descending coronary artery cannulas. Six sheep (ischemic group) were observed in a protocol of five periods, each of 2 hr duration: baseline, left atrial pressure (PLA) increased by mitral valve obstruction, return to baseline, reduced coronary flow, and reduced coronary flow plus increased PLA. Five sheep (control group) were studied in an identical protocol except that coronary flow was not reduced. PLAS were equal in the second and fifth periods. Lung lymph flow QL and protein clearance (QL times the lymph-to-plasma protein concentration ratio) normalized to second baseline were greater during ischemia than in the comparable control period, and clearance was also greater during the second increased-pressure period. We conclude that reduced coronary flow is related to sustained, significant increases in lung vascular transport at elevated as well as at normal vascular pressures.

Animals↗
PubMed1985

MR imaging parameters in the study of lung water. A preliminary study.

The use of magnetic resonance (MR) to evaluate lung water is made difficult by several factors: paucity of proton signal from normal lung, respiratory and cardiac motion, and long relaxation times of lung fluids. To optimize scanning parameters for this use, and to test MR's ability to detect and quantitate regional and temporal variations in signal intensity in hydrostatic pulmonary edema, in vivo experiments were performed with a 0.5 tesla whole body MR imaging device. Human volunteers were studied in prone and supine positions using spin echo technique (TE = 30 msec) with varying TR, and with respiratory and cardiac gating. In addition, sedated, intubated, chronically prepared sheep were paralyzed to control extraneous motion and allow the use of a high frequency ventilator, thereby eliminating respiratory gating. Elevated pulmonary hydrostatic pressure was induced in these sheep by inflation of a left atrial balloon. Relative signal intensity from the lung rises with lengthening TR. Cardiac gating diminishes motion artifact, but masks extravascular water by enhancing signal from slowly flowing blood by an average of 44%. A gravity-dependent gradient of signal intensity predictably shifts in supine and prone positions. The use of longer TRs, respiratory gating, and cardiac gating all proportionally prolong data acquisition times to an objectionable degree. Without the use of gating, a gradual rise in relative signal intensity is seen in the sheep lung following the establishment of elevated hydrostatic pressure in the pulmonary circuit, and is most pronounced in the dependent portion of the lung.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1985

Relation of blood-free to blood-inclusive postmortem lung water measurements in sheep.

Our purpose was to see if the postmortem weight ratio of extravascular lung water to blood-free dry lung (blood-free ratio) was related to similar ratios in blood-inclusive lung and in blood. We developed linear regressions of blood-free ratio on ratios for blood-inclusive lung and blood together and for blood-inclusive lung alone for 73 sheep studied under 11 different protocols and for two subgroups of sheep, one with plasma space expansion and the other without expansion. The relation of ratios of blood-free to blood-inclusive lungs was different between the two subgroups. Although all regressions were highly correlated, the fits of the blood-free ratio on ratios for blood-inclusive lung and blood together were better than for blood-inclusive lung alone. The mean error of prediction of extravascular lung water for all sheep was significantly less for the regression of blood-free ratio on ratios for blood and blood-inclusive lung together (11 g) than for blood-inclusive lung alone (18 g). This study shows that weights of lung homogenate and blood samples before and after simple oven drying can be used to provide accurate inexpensive estimates of postmortem extravascular lung water.

Animals↗
PubMed1985

Amelioration of the deleterious effects of platelets activated during cardiopulmonary bypass. Comparison of a thromboxane synthetase inhibitor and a prostacyclin analogue.

Thrombocytopenia and platelet dysfunction are commonly seen after cardiopulmonary bypass. In addition, the microvascular bed of ischemic myocardium is a potent stimulus for platelet deposition and microvascular plugging. Thus, it would appear theoretically advantageous to provide pharmacologic protection of platelets by inhibiting their response to activating agents and thereby preventing their loss into the extracorporeal circuit; this would further inhibit myocardial platelet deposition and the deleterious effects therein. Twenty-one mongrel dogs were placed on cardiopulmonary bypass with 30 minutes of normothermic global ischemia. They were randomly assigned to receive pretreatment with an infusion of saline (control, n = 8), a thromboxane synthetase inhibitor (RO-22-4679, n = 5), or a prostacyclin analogue that does not produce hypotension (ZK 36,374, n = 8). The platelet count in those animals treated with ZK 36,374 was significantly higher at the end of the experiment than in the control group (102.8 +/- 10.7 X 10(3) versus 69.7 +/- 10.6 X 10(3), p less than 0.01); the animals treated with RO-22-4679 had a platelet count between the other two groups (92.8 +/- 14.8 X 10(30)), which was not significantly different from either. Myocardial platelet deposition was measured with indium 111-labeled platelets. Those animals treated with ZK 36,374 had a much lower level of platelet deposition than the group of controls; again the RO-22-4679 group had values between the other two. Finally, myocardial blood flow after global ischemia and cardiopulmonary bypass, measured with radioactive microspheres, was significantly higher in the ZK 36,374 group than in the control group. We conclude that ZK 36,374 prevents platelet consumption during cardiopulmonary bypass over and above that seen with inhibition of thromboxane synthesis alone. It also prevents deposition of platelets into the myocardium after global ischemia and we presume by that mechanism increases myocardial blood flow.

Animals↗
PubMed1985

Pathophysiology of chronic cyanosis in a canine model. Functional and metabolic response to global ischemia.

To investigate the pathophysiology of chronic cyanosis, we subjected 14 adult mongrel dogs to diversion of the inferior vena cava to the right inferior pulmonary vein. This produced a mean oxygen tension of 42 +/- 2 mm Hg and a calculated right-to-left shunt of 52.0% +/- 3.9%. These animals (Group C) and 15 normal dogs (Group N) were subjected to cardiopulmonary bypass with 20 minutes of normothermic global ischemia. Functional indices studied were rate of rise of left ventricular pressure and the end-systolic pressure/volume ratio. Metabolic status was assessed by obtaining transmural myocardial biopsy specimens for measurement of adenosine triphosphate content. Myocardial blood flow was measured with radiolabeled microspheres. There were no significant differences between Group C and Group N in either functional index or blood flow measurement prior to global ischemia. At 45 minutes after ischemia, Group N animals had a significantly greater rate of rise of left ventricular pressure (at a left ventricular end-diastolic pressure of 0, 5, 10, and 15 mm Hg, p less than 0.025 to 0.05) and subendocarial perfusion (endocardial/epicardial flow ratio 0.961 +/- 0.037 versus 0.815 +/- 0.021, p less than 0.01). At 90 minutes after ischemia, Group N animals exhibited a significantly higher end-systolic pressure/volume ratio (4.9 +/- 0.7 versus 3.0 +/- 0.4 mm Hg/ml, p less than 0.05), rate of rise of left ventricular pressure (at an end-diastolic pressure of 0 to 20 mm Hg, p less than 0.005 to 0.05), and endocardial/epicardial flow ratio (1.065 +/- 0.046 versus 0.829 +/- 0.059, p less than 0.01). No differences in adenosine triphosphate content were found at any sampling period. The Group C left ventricles exhibited no hypertrophy but were significantly dilated compared to Group N (38.8 +/- 0.3 versus 30.1 +/- 0.2 mm, p less than 0.05). Inferior vena cava to pulmonary vein diversion produces cyanosis with left ventricular dilatation but without hypertrophy. It is proposed that abnormal loading characteristics of the left ventricle are responsible for the functional derangements that result from global ischemia.

Adenosine Triphosphate↗
PubMed1984

Effects of blood flow reduction and lymphatic ligation on coronary transport in dogs.

We studied the effects of reduced-flow coronary ischemia and coronary lymphatic ligation on transcapillary movement of albumin. We infused 125I-albumin intravenously into four groups of five anesthetized, open-chest dogs in which external carotid-to-coronary arterial cannulas had been placed. One group was subjected to both lymphatic ligation and ischemia; a second group to lymphatic ligation only; a third group ischemia only; and the fourth was a control group. After 1 hr, 85Sr-microspheres were injected into the cannula. After 2 hr, the animals were sacrificed. Extravascular albumin activities in heart sections that were perfused from the cannula were normalized to extravascular albumin in normal-flow regions. This variable was greater in the lymph-ligated and ischemic groups than in the control, and greater in the combined lymph-ligated and ischemic group than any other group. Relative increase in coronary vascular resistance over the protocol interval correlated significantly with normalized albumin content in the cannulated sections. Although both ischemia and lymph ligation lead to increased extravascular albumin accumulation, their mechanisms are different. Increased extravascular albumin after ischemia may be due to increased capillary permeability.

Albumins↗
PubMed1984

Hepatitis B virus infections transmitted from retarded children to their families during brief home exposure.

Hepatitis B virus (HBV) infection is endemic among institutionalized retarded patients, who usually have mild, anicteric hepatitis following nonparenteral exposure. We evaluated the risk of HBV infection (as evidenced by serologic studies) among their contacts, including noninstitutional caretakers, during brief home exposure. Caretakers shaved, bathed, and changed diapers for five patients during home visits or foster home placements. Seven of the 14 caretakers, who were exposed for 3-12 months, developed antibodies (anti-HBc and/or anti-HBs). A mother and her daughter's caretaker were found to have asymptomatic acute HBV infection, and the mother developed antibodies to HBs, HBc, and HBe. In a second household, another caretaker became anti-HBs-positive. Only one of nine play contacts and none of seven casual contacts had markers of past or present HBV infection. The study was a unique opportunity to retrospectively and prospectively monitor HBV transmission. Our results show that noninstitutional caretakers deserve the protection of HBV vaccine to diminish the potential for chronic infection and transmission of HBV infection.

Adult↗
PubMed1984

Acute synovitis caused by an organism of the Rhodochrous taxon.

A 36-year-old man with systemic lupus erythematosus developed synovitis of the right wrist caused by an organism of the Rhodochrous taxon. The capacity of this pathogen to produce a granulomatous inflammatory reaction in human tissues is discussed. The isolate was sensitive to chloramphenicol, gentamicin, carbenicillin and colistin in in-vitro tests and the infection responded promptly to treatment with chloramphenicol.

Actinomycetales↗
PubMed1984

Tracer exchange in the normal and ischemic coronary circulation.

Proper function of the coronary blood-tissue exchange system may be important in the preservation of myocardium threatened by ischemia. We have undertaken studies aimed at elucidating the functions of this system under baseline and ischemic conditions. The exchange of [14C]sucrose between the coronary capillaries and extravascular space has been studied with the multiple-tracer method. Protein transport has been examined by measuring the deposition of labeled albumin and by collecting cardiac lymph. Results indicate that reduced-flow ischemia decreases functioning capillary surface area but increases permeability to small molecules and protein. Hyaluronidase and adenosine can restore flow after partial occlusion of the coronary artery. However, only hyaluronidase restores capillary surface to its baseline value. Thus, ischemic effects on exchange are not controlled merely by hemodynamic factors. Reduced-flow ischemia in the heart can induce a vascular permeability change in the lung circulation. We conclude that capillary and interstitial transport are altered significantly by ischemia. Preservation of the proper function of these processes may be important in protecting the ischemic myocardium.

Animals↗
PubMed1983

Effects of coronary flow reduction on lung vascular tissue transport in sheep.

This study was performed to measure the effects of a sustained reduction in coronary flow on lung lymph flow and protein content. Ten halothane-anesthetized sheep with cannulated lymphatic vessels were provided with a carotid-to-left anterior descending coronary artery cannula containing an electromagnetic flowmeter. One group of five animals was observed at base line and after coronary flow was reduced to 38% of base line. A second group of five animals acted as controls and was observed at base line, for 111 min of increased left atrial pressure, and a second period of normal pressures. Sustained coronary flow reduction led to significant increases in pulmonary arterial pressure, left atrial pressure, lymph flow, total protein lymph-to-plasma concentration ratio (L/P), and protein lymph clearance (L/P X lymph flow). Analysis of the pressure, lymph, protein, and indicator data with a two-pore model of the microvascular barrier showed that the observations were consistent with the concept that coronary flow reduction decreased functioning lung capillary surface but increased the size of the large pore and the number of small pores relative to the number of larger pores. Control studies showed increases in lymph flow and decreases in L/P with increased pressure but no significant changes in any variable between the first and second period of normal pressures. We conclude that coronary flow reduction increases lung vascular-tissue transport by decreasing the resistance of the microvascular barrier to protein and fluid movement. However, increased pressure secondary to left ventricular dysfunction plays a role in the magnitude of this response.

Animals↗
PubMed1983

Kinetics and imaging of indium-11-labeled autologous platelets in experimental myocardial infarction.

The kinetics of accumulation and the external imaging patterns of indium-111-labeled platelets infused in a dog model of left anterior descending coronary artery occlusion with reperfusion were studied. The effects of infarct age and regional residual myocardial blood flow upon platelet accumulation were quantified, and the capacity of indium-111 platelets to image the experimental infarction was evaluated qualitatively. The endocardial accumulation of indium-111 platelets occurred primarily in infarct zones with residual blood flow less than 0.6 times normal and was maximal (24.98 +/- 2.76 times normal) in the lowest blood flow zone (less than 0.1 times normal). Indium-111 platelet accumulation in the epicardium occurred in the regions with blood flow less than 0.6 times normal and was maximal (17.83 +/- 1.20 times normal) in the lowest blood flow zone (less than 0.1 times normal). The maximal endocardial and epicardial platelet accumulation occurred 24 hours after reperfusion and was significantly decreased at 48 hours. In vivo cardiac images revealed discrete areas of increased myocardial radioactivity uptake in the anterior wall of dogs 24 hours after reperfusion. All images 48 hours after reperfusion were negative. Thus, in the experimental setting, indium-111 platelets allow quantification of platelet accumulation after myocardial infarction at a tissue level and provide a noninvasive means of in vivo imaging of reperfused infarcted myocardium.

Animals↗
PubMed1982

Effect of albumin and mannitol on organ blood flow, oxygen delivery, water content, and renal function during hypothermic hemodilution cardiopulmonary bypass.

The present study was designed to determine if the addition of albumin or mannitol to the priming solution of the pump oxygenator would diminish edema in organs, without diminishing some of the beneficial effects of hemodilution on blood flow and renal function. Tissue blood flow (15 mu spheres), water content, and renal clearances were determined in 8 animals during cardiopulmonary bypass. A 2(2) factorial, completely fixed experimental design was used. All animals were placed on cardiopulmonary bypass with hemodilution (hematocrit 25 +/- 2%) and hypothermia (25 degrees +/- 1 degree C). Albumin decreased flow to the midmyocardium of the left ventricle and to the spleen, and increased flow to the inner cortex of the kidney. Albumin caused decreased urine flow and decreased urine sodium, and also diminished renal osmolar, sodium, and free-water clearances. both mannitol and albumin decreased lung water. Mannitol decreased water content of the outer renal cortex, and decreased flow to the inner cortex and medulla of the kidney and to the spleen. Mannitol had no significant effect on urine flow, renal plasma flow, or renal clearances. Neither albumin nor mannitol had any effect on water content of the intestine, stomach, liver, or myocardium where the greatest accumulation of water occurs with hemodilution. The effect of albumin on renal function is potentially deleterious during cardiopulmonary bypass because it decreases urine flow, and osmolar and free-water clearance.

Animals↗
PubMed1982

IgA interaction with the asialoglycoprotein receptor.

IgA present in normal human serum reacts with the hepatic receptor specific for asialoglycoproteins as demonstrated by inhibition of receptor-mediated erythroagglutination. Inhibition is reversibly abolished by the oxidation of the galactose or N-acetylgalactosamine residues of IgA with galactose oxidase. The site of receptor recognition appears to be the O-glycosidically linked oligosaccharides present on the hinge region of the IgAI subtype of IgA. The demonstration of a specific binding, in vitro, of IgA by the hepatic receptor suggests that the uptake of polymeric IgA by the liver in vivo may be mediated by this reaction.

Animals↗