Biomedical subjects

G Coates

Publications and source records attributed to G Coates.

At least 91 records · Page 5Linked to original sources

PubMed1985

Central dopaminergic activity influences rats ability to exercise.

Rats were run to exhaustion on a motor driven treadmill. Apomorphine given to intact rats prolonged the time to exhaustion. Apomorphine given to 6-hydroxydopamine lesioned rats also prolonged the time to exhaustion. Intracerebroventricular 6-hydroxydopamine alone reduced the time to exhaustion. Clonidine given to these animals had no effect. We suggest that central dopaminergic activity influences rats ability to exercise.

Animals↗

PubMed1985

Management of cancer pain. A practical approach.

One in five deaths in Australia is due to cancer. Pain is an important symptom in many of these patients, but it is often either unrelieved or poorly controlled. Misconceptions about the nature of cancer pain and its control are detailed, and the practical management of these patients is discussed in the light of personal experience. Proper use of older therapeutic methods is still important, as recent advances allow better results only in a minority of cases. Special attention is given to the use of regular oral doses of morphine. Many of the interacting factors affecting pain perception are considered, so that the sense of impotence in those faced with the management of a progressive incurable disease may be reduced through an understanding of the causes of pain and its correct management.

Analgesics↗

PubMed1985

Pulmonary thromboemboli after neonatal asphyxia.

Two surviving neonates with pulmonary thromboembolism, diagnosed by ventilation-perfusion lung scan, are described. Both infants had respiratory distress, and one had features consistent with persistent pulmonary hypertension of the neonate. These reports demonstrate that substantive pulmonary emboli can occur in neonates and may not be recognized without an appropriate level of clinical suspicion.

Asphyxia Neonatorum↗

PubMed1985

Ventilation scanning with technetium labeled aerosols. DTPA or sulfur colloid?

We have compared the distribution in the lungs of submicronic aerosols of either Tc-99m sulfur colloid or Tc-99m DTPA immediately after inhalation with the distribution 20 minutes later in 83 patients. Thirty-two of the 83 patients were active smokers. Of the 28 smokers who received Tc-99m DTPA aerosol, the total lung count fell by a mean of 27 +/- 14% between the 0 and 20 minute image. Eleven of these patients also had a major change in distribution of isotope during this time. In the nonsmoking patients total lung counts from Tc-99m DTPA fell by only 16 +/- 8% and none had a major change in distribution pattern. None of the smoking or non-smoking patients who received Tc-99m sulfur colloid had a significant change in count rate or distribution pattern over 20 minutes. The effects on the ventilation images of these rapid changes in count rate and distribution pattern after Tc-99m DTPA aerosol can be minimized by completing the ventilation study as quickly as possible after inhaling Tc-99m DTPA or by using a nondiffusible agent such as Tc-99m sulfur colloid.

Aerosols↗

PubMed1985

Bradykinin is degraded in hypoxic lungs and does not affect epithelial permeability.

To investigate the effect of intravenous infusions of bradykinin (BK) on the permeability of the hypoxic pulmonary epithelium to small solutes, experiments (n = 7) were performed in yearling sheep with chronic vascular catheters. Sheep were anesthetized, intubated, paralyzed, and ventilated. After establishing stable and normal base-line pulmonary hemodynamics and blood gas tensions, the lungs were insufflated with a submicronic aerosol of technetium-99m-labeled diethylenetriaminepentaacetate (99mTc-DTPA, mol wt = 492). Radioactivity arising from the right hemithorax was measured by an NaI probe with a parallel-holed collimator. The base-line pulmonary clearance rate (k) for 99mTc-DTPA was 0.51 +/- 0.09% (SE)/min, while the sheep were ventilated with a fractional concentration of inspired O2 (FIO2) of 0.5 [arterial partial pressure of O2 (PaO2) = 196 +/- 11.4 (SE) Torr]. Clearance of 99mTc-DTPA was unaffected by hypoxia alone or BK infusions in nonhypoxic lungs. The combination of an intravenous infusion of BK at either 1.2 (n = 3) or 2.4 micrograms . kg-1 . min-1 (n = 4) and alveolar hypoxia [FIO2 = 0.11, PaO2 = 28 +/- 1.6 (SE) Torr] did not affect pulmonary clearance of 99mTc-DTPA [k = 0.43 +/- 0.08% (SE)/min]. In contrast, a 0.05-ml/kg intravenous infusion of oleic acid increased clearance 10-fold in one sheep. During combined hypoxia and BK infusion the pulmonary arterial BK concentration (radioimmunoassay) increased from 0.82 +/- 0.16 (SE) to 7.05 +/- 1.86 ng/ml (P less than 0.001), but the systemic arterial concentrations were unchanged [0.67 +/- 0.19 (SE) to 0.66 +/- 0.09 ng/ml].(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1985

Diagnostic value of ventilation-perfusion lung scanning in patients with suspected pulmonary embolism.

Differing opinions about the value of ventilation-perfusion lung scanning have created controversy concerning the correct approach to the diagnosis of pulmonary embolism. In a prospective study of 305 consecutive patients with clinically suspected pulmonary embolism and abnormal perfusion lung scans, we evaluated the role of ventilation-perfusion lung scanning, pulmonary angiography, and objective testing for venous thrombosis in the diagnostic process. Segmental or greater perfusion defects with ventilation mismatch have a high probability (86 percent) of pulmonary embolism. Contrary to current clinical practice, however, the approach of ruling against pulmonary embolism by a "low probability" scan pattern is incorrect, even with an improved technique for ventilation imaging; the frequency of pulmonary embolism in these patients ranged from 25 to 40 percent. Objective testing for venous thrombosis provides a practical alternative to performing pulmonary angiography in the diagnostic work-up; by providing an endpoint for commencing anticoagulant therapy, a positive result obviates the need for further testing in 20 to 30 percent of patients.

Adolescent↗

PubMed1985

Hypoxia-induced vasopressin release and coagulopathy in a normal subject.

Humans exposed to hypoxia usually increase their plasma procoagulant VIII activity (VIII:C) with no change in the concentration of VIII related antigen (VIIIR:Ag). This case report describes an apparently normal subject who developed marked qualitative and quantitative changes in all components of the factor VIII complex while inhaling an 11% oxygen/balance nitrogen gas mixture for 2 h. Blood from fresh venepunctures was drawn at baseline, during and after exposure to hypoxia for the following: a partial thromboplastin time, a prothrombin time, fibrin monomer, factor VIII:C, VIII procoagulant antigen (VIII:CAg); ristocetin cofactor activity (VIIIR:Co); VIII von Willebrand factor (VIII:vWF) multimer pattern; and arginine vasopressin. During hypoxia VIII:C, VIII:CAg, VIIIR:Ag and VIIIR:Co increased 4 to 5 fold; the VIII:vWF multimer pattern showed increasing low molecular weight complexes, fibrin monomer appeared and arginine vasopressin (AVP) levels increased from 5.5 pg . ml-1 to 73.8 pg . ml-1. These changes are compatible with both the release of the VIIIR:Ag by AVP and protease induced fragmentation of the VIII complex.

Arginine Vasopressin↗

PubMed1985

Fluosol-DA causes pulmonary hypertension and increased lung lymph flow in unanesthetized sheep.

Test doses (0.5 ml) of the perfluorochemical blood substitute Fluosol-DA causes pulmonary hypertension in some patients. To investigate this phenomenon we infused Fluosol-DA into unanesthetized sheep with chronic vascular catheters on ten occasions. In six of these experiments lung lymph flow was measured. Since other fluorochemical blood substitutes alter the coagulation cascade we also sampled blood to perform coagulation screening tests and look for evidence of thrombin generation as assessed by the survival of 125I labelled sheep fibrinogen. Test doses (0.5 ml) of Fluosol-DA resulted in transient but marked pulmonary hypertension in nine of ten experiments (17 +/- 1.2 SE to 43 +/- 3.9 SE torr). Cardiac output decreased by an average of 30%, and lung lymph flow transiently increased without a change in the lymph to plasma protein concentration (L/P) ratio in five of six experiments. When 50 ml of Fluosol-DA was administered one hour later the pulmonary hypertension was more prolonged but less severe (18 +/- 1.0 SE to 34 +/- 3.2 SE torr). Lymph flow again increased without a change in the L/P ratio for protein. The activated partial thromboplastin and prothrombin times, and survival in plasma of 125I labelled sheep fibrinogen were unaffected by administration of Fluosol-DA. We conclude that Fluosol-DA causes pulmonary hypertension in sheep and increases lung lymph flow. This results from vasoconstriction of the pulmonary vessels and subsequent recruitment of the pulmonary microvasculature and not from thromboembolic phenomena.

Animals↗

PubMed1984

Pulmonary epithelial permeability in hyaline-membrane disease.

Neonatal hyaline-membrane disease is complicated by pulmonary edema, yet left atrial pressures are normal. Alveolar-capillary-membrane permeability may therefore be increased. To assess pulmonary epithelial permeability, we measured the pulmonary clearance and half-life of aerosolized 99mTc-diethylenetriamine pentacetate (99mTc-DTPA) on 31 occasions in 15 intubated premature infants with hyaline-membrane disease. Three infants with respiratory failure due to other diseases were studied on four occasions. All studies of infants with hyaline-membrane disease that were performed in the first 72 hours of life demonstrated a biphasic clearance curve with a rapid-phase half-life of 1.6 +/- 0.6 minutes (mean +/- S.D.). As these infants recovered, the curve became monophasic with a half-life of 56.0 +/- 32.1 minutes. Two infants remained dependent on oxygen and ventilator support and had persistent biphasic curves with a rapid-phase half-life of 1.5 +/- 0.7 minutes. All infants without hyaline-membrane disease had monophasic curves with a half-life of 65.4 +/- 33.6 minutes. Using a similar technique, we observed that newborn lambs and piglets have a monophasic pulmonary clearance of 99mTc-DTPA (114 +/- 59 minutes in lambs and 52.5 +/- 16.3 minutes in piglets). We conclude that the lungs of neonates with hyaline-membrane disease are abnormally permeable to small solutes and that this abnormality persists in infants with subsequent chronic lung disease.

Aerosols↗

PubMed1984

Quantitative ventilation-perfusion lung scans in infants and children: utility of a submicronic radiolabeled aerosol to assess ventilation.

The quantitative assessment of regional pulmonary ventilation and perfusion provides useful information regarding lung function. Its use in infants and young children, however, has been minimal because of practical and technical limitations when the distribution of ventilation is assessed by radioactive gases. In 16 infants and children we used an inexpensive commercially available nebulizer to produce a submicronic aerosol labeled with 99mtechnetium-diethylenetriamine pentacetic acid to assess ventilation quantitatively, and intravenous injections of 99mtechnetium-labeled macroaggregates of albumin to assess pulmonary perfusion quantitatively. Studies were safely completed in both ambulatory and critically ill patients, including two premature infants who had endotracheal tubes in place for ventilatory support. No sedation or patient cooperation is required. This technique enables any department of nuclear medicine to measure regional pulmonary ventilation and perfusion in infants and children.

Adolescent↗

PubMed1984

Hypoxia alters blood coagulation during acute decompression in humans.

Acute decompression is associated with a shortening of the activated partial thromboplastin time (aPTT). This study was performed to examine whether this change in aPTT results from hypoxia or hypobaria. We exposed healthy adults on three separate occasions to 2 h of 1) hypoxic hypobaria (410 Torr, n = 5), 2) hypoxic normobaria (fractional inspired O2 tension = 0.11, n = 4), or 3) normoxic hypobaria (410 Torr breathing supplemental O2, n = 5). The aPTT shortened during hypoxic hypobaria and hypoxic normobaria (P less than 0.05) but was unchanged during normoxic hypobaria. The prothrombin and thrombin times, hematocrit, and concentrations of fibrinogen, total plasma protein, and fibrinogen-fibrin fragment E were unchanged. During hypoxic hypobaria biologic levels of prekallikrein, high-molecular-weight kininogen, and factors XII, XI, X, VII, V, and II were unchanged, but procoagulant VIII (VIII:C) increased 50% without an increase in VIII-related antigen levels (VIIIR:Ag). Fibrin monomer was not detected in any group. In one subject who became ill after 1.5 h of hypoxic normobaria aPTT shortened by 10 s; the platelet count decreased by 93,000/mm3; VIII:C increased fivefold, but VIIIR:Ag only increased three-fold. We conclude that it is the hypoxia which shortens aPTT during acute decompression to 410 Torr and speculate that it results from an increase in plasma VIII:C-like activity.

Adult↗

PubMed1984

Measurement of pulmonary clearance of radioaerosol using a portable sodium iodide probe.

To determine whether a portable sodium iodide (NaI) probe could provide a valid measure of the pulmonary half-life (T1/2) of aerosolized technetium-99m-diethylenetriaminepentaacetate (99mTc-DTPA, mol wt = 492) in small chests, we measured pulmonary clearance in rabbits using a gamma-scintillation camera and the portable probe. In 10 experiments the lungs of New Zealand White rabbits were insufflated with aerosolized 99mTc-DTPA (0.6 mum aerodynamic mass median diameter) and then simultaneously imaged with the gamma-camera and the probe positioned over the upper right lung. In an additional 12 experiments, alveolar-capillary membrane permeability was increased by either intratracheal instillation of 0.1 N hydrochloric acid (HCl) or intravenous injection of 100 mg/kg of oleic acid. All animals tolerated the procedure. There was a significant decrease in pulmonary T1/2 in both the HCl group (53.4 +/- 10.4 min, mean +/- SE) and the oleic acid group (14.7 +/- 2.3 min) when compared with control (127.5 +/- 18.1 min). When we compared the T 1/2 of the right lung determined by the gamma-camera with that measured by the probe, the correlation coefficient was 0.95. Potential nonpulmonary contributions to thoracic radioactivity were not significant. We conclude that a portable NaI probe is a valid means of determining T 1/2 of 99mTc-DTPA in small chests when compared with a gamma-camera and can detect increases in the permeability of the alveolar-capillary membrane to small solutes.

Aerosols↗

PubMed1984

Effects of exercise on lung lymph flow in sheep and goats during normoxia and hypoxia.

Vigorous exercise causes a marked increase in cardiac output with only a minimal increase in measureable pulmonary vascular pressures. These changes in pulmonary hemodynamics should affect lung water and solute movement. On nine occasions, we measured the effect of normoxic exercise on lung lymph flow in four sheep and two goats with chronic lymph fistulas (wt = 15-25 kg). In addition, lymph flow was also measured on five occasions in sheep during exercise at reduced barometric pressures (430 and 380 mmHg). During normobaria, the animals ran at 3-5 km/h with 0-10% elevation of the treadmill for 15 to 85 min. Exercise on average caused a 100% increase in cardiac output, a 140% increase in lung lymph flow, and a slight but significant reduction in lymph to plasma concentration ratio (l/p) for total protein and albumin (mol wt = 70,000). There was a significant linear correlation between lymph flow and cardiac output (r = 0.87, P less than 0.01). There was no change in l/p for IgG (mol wt = 150,000) or IgM (mol wt = 900,000) and no significant change in mean pulmonary arterial (Ppa) or mean left atrial (Pla) pressures. Transition from normobaria to hypobaria caused an increase in Ppa but no change in Pla, cardiac output, or lymph flow. Exercise during hypobaria caused increases in lymph flow that were qualitatively similar to changes observed during normobaric exercise: there was a 60% increase in cardiac output, a 90% increase in lymph flow, and an 11% reduction in l/p for total protein. There was no change in l/p for albumin, IgG, or IgM, and no further change in Ppa. The increased lymph flow during normoxic and hypobaric exercise is best explained by an increase in pulmonary vascular surface area for fluid and protein exchange. Our results suggest that the normal ovine lung has the potential to nearly triple the amount of perfused microvascular surface area. This speculation is relevant to the interpretation of lymph flow data from other experiments.

Aerobiosis↗

PubMed1983

Rapid identification of correctly located intracerebroventricular cannula in the rat.

We describe a radiographic technique to identify a correctly located cannula in the ventricular system of the rat brain during life. A suspension of thorium dioxide was infused into the left lateral ventricle through a cannula placed in the brain under stereotaxic guidance. Correctly located injections were identified by the presence of a distinct thorium shadow on lateral X-ray of the in situ brain. When 6-hydroxydopamine was co-injected with thorium the resultant depletion of striatal dopamine and the changes in a conditioned avoidance responses were correlated with the degree of spreading of thorium through the ventricular system.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1983

Hypobaric hypoxia does not affect lung fluid or protein exchange in awake adult sheep at rest.

We measured pulmonary artery (Ppa) and left atrial (Pla) pressures, lung lymph flow, and lymph/plasma protein concentrations in four adult sheep at a barometric pressure of 380 Torr (1 Torr = 133.322 Pa) for 22 h. Hypobaric hypoxia caused an immediate increase in Ppa from 20 to 39 Torr. There was no significant change in Pla, lymph flow, or lymph protein concentrations. We conclude that hypobaric hypoxia does not affect lung fluid or protein exchange in awake adult sheep at rest.

Animals↗

PubMed1983

Platelets and leukocytes in the lungs after acute hypobaric hypoxia.

To determine if decompression from sea level causes aggregation and embolization of platelets or leukocytes to the lungs, we have measured the accumulation of 51Cr-labeled platelets or 111In-labeled leukocytes in the lungs of rabbits decompressed to 440 or 350 Torr for 18 or 40 h. To be certain that any increased accumulation of labeled platelets (or leukocytes) in the lungs was not just caused by an increased pulmonary blood volume we also labeled the rabbits red blood cells with 59Fe. There was no detectable accumulation of labeled platelets in the lungs on decompression. In control animals there were 22 times as many labeled leukocytes in the lungs as could be accounted for by the volume of blood in the lungs. In experimental animals at 326 Torr for 18 h this figure was reduced to 13.6. Hypobaric hypoxia caused an increase in circulating granulocytes from a mean of 3.3 +/- 1.6 X 10(9)/l to 5.3 +/- 2.1 X 10(9)/l. (P less than 0.005). Our results suggest that decompressions to 6,100 m for 18 h does not cause platelet sequestration in the lungs but does cause a significant reduction in leukocytes in the lungs and a peripheral granulocytosis.

Acute Disease↗

PubMed1983

Assessment of coagulation cascade during air microembolization of the lung.

Experiments were performed to determine whether activation of the coagulation cascade was required for pulmonary vascular permeability to increase during microembolization of the lung. For 30-45 min air microemboli were intravenously infused (0.05-0.10 ml X kg-1 X min-1) into awake sheep with chronic lung-lymph fistulas and anesthetized mongrel dogs. During embolization the pulmonary arterial pressure increased, and O2 partial pressure (PaO2) fell by more than 20 Torr (P less than 0.01). Subsequently lymph flow nearly tripled without a change in the lymph-to-plasma protein concentration ratio. Partial thromboplastin and prothrombin times, biological activity of antithrombin III, and circulating concentration of 125I-labeled dog or sheep fibrinogen did not change during or following air infusion. In two additional sheep an intravenous infusion of thrombin at 0.6 U X kg-1 X min-1 for 15 min resulted in a 20% decrease in 125I-labeled sheep fibrinogen concentration without a change in pulmonary arterial pressure or PaO2. We conclude that air microembolization can increase permeability to water and protein without a detectable activation of the coagulation cascade in the sheep or dog.

Animals↗

PubMed1983

The effects of intravenous infusion of saline on lung density, lung volumes, nitrogen washout, computed tomographic scans, and chest radiographs in humans.

In this study we examined the effect of a 15% increase in extracellular fluid volume on lung density, lung volumes, nitrogen washout, chest radiographs and computerized tomographic (CT) scans of the thorax in 5 volunteers. The objective of the study was to determine the sensitivity of these techniques in detecting small changes in lung water. Lung density was measured by a gamma ray Compton scatter technique and with an Ohio nuclear delta 2020 CT scanner. We measured or derived functional residual capacity, residual volume (RV), vital capacity (VC), and total lung capacity by helium dilution. Single-breath nitrogen washout was used to measure closing volume and the slope of phase III nitrogen washout (delta N2). Chest radiographs were taken in the posteroanterior and lateral projections. With the CT scanner we obtained slices 1 cm thick through the bases of the lungs and at 6 and 12 cm up from the bases. All these measurements were made before and 20 to 90 min after the intravenous infusion of 30 ml/kg body weight of warm saline over a period of 20 min. The most striking findings were a 24% increase in delta N2, a 14% increase in RV, and a 4.5% decrease in VC. Chest radiographs and the CT scans showed an increase in the size of the azygos veins. There was no change in Compton scatter density or the CT numbers. These results suggest that (1) tests of small airway function, such as RV and delta N2, are more sensitive than radiographic techniques to small increases in lung water, (2) there is some protection of the lung to increases in extracellular fluid volume.

Adult↗