PubMed HealthSearch

Biomedical subjects

A T Rogers

Publications and source records attributed to A T Rogers.

At least 19 recordsLinked to original sources

alpha-Bungarotoxin binding sites in rat hippocampal and cortical cultures: initial characterisation, colocalisation with alpha 7 subunits and up-regulation by chronic nicotine treatment.

High density neuronal cultures from rat E18 hippocampus and cortex have been characterised with respect to cholinergic binding sites. No specific binding of [3H]nicotine or [3H]cytisine to live cells in situ was detected although the limit for detection was estimated to be 30 fmol/mg protein. Muscarinic binding sites labelled with [3H]QNB were present at a density of 0.75 pmol/mg protein. [125I]alpha-Bungarotoxin (alpha Bgt) bound to hippocampal cultures with a Bmax of 128 fmol/mg protein and a Kd of 0.6 nM; cortical cultures expressed five times fewer [125I]alpha-Bgt binding sites. Fluorescence cytochemistry with rhodamine-alpha-Bgt indicated that 95% of hippocampal neurons were labelled, compared with only 36% of cortical neurons. Average densities of 4 x 10(4) and 2 x 10(4) binding sites/cell were calculated for hippocampal and cortical cultures, respectively. Double labelling experiments with mAb307 (which recognises the rat alpha 7 nicotinic receptor subunit) and rhodamine-alpha-Bgt gave coincident labelling patterns, supporting the correlation between the alpha 7 subunit and Bgt-sensitive neuronal nicotinic receptor. Treatment of hippocampal cultures with 10 microM nicotine for 14 days elicited a 40% increase in the numbers of [125I]alpha-Bgt binding sites, mimicking the up-regulation observed in in vivo studies. Primary cultures offer a useful in vitro system for investigating the expression and regulation of brain alpha-Bgt-sensitive receptors.

Animals

The estimation of administered activity of krypton-81m for lung ventilation studies.

Measurement or estimation of the activity of krypton-81m administered to a patient during lung ventilation imaging is difficult, due to the short half-life and continuous delivery via pipework, and no satisfactory method exists. Calculations based on generator activity have the disadvantages that this activity may not be accurately known and that not all activity eluted is inhaled by the patient. The aim of this study was to develop a simple method for estimating the administered activity from the number of counts in each patient image. A formula based on the ratio of counts in 81mKr and technetium-99m lung ventilation and perfusion images was developed and reduced so that administered activity could be directly calculated from the total 81mKr counts, the 99mTc count rate, the administered activity of 99mTc and a constant representing the ratio of counts expected from equal activities of each radioisotope. The formula allows a direct calculation from the image acquisition data following an initial set of experimental work to establish the constant for a particular gamma camera and collimator system.

Administration, Inhalation

A comparison of computed tomography practice in 1989 and 1991.

In December 1991, the National Radiological Protection Board (NRPB) published the results of national surveys of the frequency, quality assurance and dosimetric aspects of computed tomography (CT) examinations carried out in hospitals in the UK in 1989. A study of the patient records at two of the original participating hospitals was undertaken to establish whether there had been any change in CT practice between the years 1989 and 1991. Aspects of examination frequency, age distribution and dose were analysed. The results showed significant variations in the patient age distributions between the sub-population studied and the larger sample used by the NRPB, and between the patient age distribution for CT examinations in the years 1989 and 1991 at the two hospitals in this study. The results also showed that in one hospital, where magnetic resonance imaging (MRI) was available and where dose reduction measures had been implemented, there was a net decrease in the collective effective dose from 1989 to 1991, whilst at the other hospital, where MRI was not available and where the introduction of dose saving strategies had been delayed, there was a substantial increase in the collective effective dose from 1989 to 1991. The possibility of continuing increases in the annual collective effective dose attributable to CT underlines the importance of local CT audit to ensure that CT doses are as low as reasonably achievable.

Adolescent

Heparin management protocol for cardiopulmonary bypass influences postoperative heparin rebound but not bleeding.

A group of 63 adult patients undergoing cardiac surgical procedures requiring cardiopulmonary bypass (CPB) were studied to examine the relationship between heparin doses administered and postoperative bleeding. Patients were randomly assigned either to receive heparin 200 U/kg and additional heparin as needed to reach and maintain an activated clotting time (ACT) greater than 400 s for CPB (group A, n = 30), or to receive heparin 400 U/kg and additional heparin as needed to reach and maintain a whole blood heparin concentration greater than 4.0 U/ml for CPB (group H, n = 33). Groups were compared for the amount of postoperative bleeding, heparin rebound, homologous transfusion requirements, and standard laboratory coagulation tests. In the last 33 patients studied, additional tests of platelet aggregation and plasma levels of beta thromboglobulin (BTG), antithrombin III, and several markers of fibrinolysis were measured and compared by group. The mean heparin dose was 28,000 +/- 4,800 U for group A and 57,000 +/- 10,700 U for group H (P less than 0.05 for group A vs. group H). At 8 and 24 h postoperatively, mediastinal drainage did not differ significantly between groups (mean 24-h drainage +/- SD = 901 +/- 414 ml in group A, 1035 +/- 501 ml in group H), nor did the incidence of transfusion with homologous blood products.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Cerebrovascular and cerebral metabolic effects of alterations in perfusion flow rate during hypothermic cardiopulmonary bypass in man.

Recent experimental and clinical investigations provide conflicting evidence regarding the effects of changes in the systemic flow rate from the pump oxygenator on cerebral blood flow and the cerebral metabolic rate of oxygen consumption. However, the results of existing clinical studies are difficult to interpret because of the confounding effects of differences in management of arterial carbon dioxide tension and use of anesthetic and vasoactive agents during cardiopulmonary bypass. To clarify the relationship among perfusion flow rate, cerebral blood flow, and cerebral metabolic rate of oxygen consumption in man during hypothermic cardiopulmonary bypass, we varied perfusion flow rate in random order to either 1.75 or 2.25 L.min-1.m-2 and studied cerebral blood flow (measured by clearance of xenon 133) and cerebral metabolic rate of oxygen consumption (estimated as the product of cerebral blood flow and the cerebral arteriovenous oxygen content difference) in patients managed with both the alpha-stat (group 1) and the pH-stat (group 2) methods of pH and arterial carbon dioxide tension adjustment. We measured the cerebral arteriovenous oxygen content difference using radial arterial and jugular venous bulb blood samples. In each patient other variables known to exert effects on cerebral blood flow and cerebral metabolic rate of oxygen consumption, including temperature, arterial carbon dioxide tension, arterial oxygen tension, mean arterial pressure, and hematocrit, were maintained constant between measurements. In both groups, mean arterial pressure at both pump flow rates was similar because of spontaneous reciprocal alterations in systemic vascular resistance, that is, as perfusion flow rate declined, systemic vascular resistance increased; as perfusion flow rate increased, systemic vascular resistance declined. Under these tightly controlled conditions, pump flow variation per se exerted no effect on cerebral blood flow or cerebral metabolic rate of oxygen consumption in either group.

Blood Flow Velocity

Sodium nitroprusside infusion does not dilate cerebral resistance vessels during hypothermic cardiopulmonary bypass.

This study determined whether sodium nitroprusside (SNP) changes cerebral vascular resistance during stable, hypothermic cardiopulmonary bypass (CPB). Cerebral blood flow (CBF) was measured using Xenon clearance in 39 patients anesthetized with fentanyl. In 25 patients (group 1), CBF was measured before and during infusion of SNP at a rate sufficient to reduce mean arterial pressure (MAP) approximately 20%. In 14 other patients (group 2), CBF was measured before and during simultaneous infusion of SNP and phenylephrine; SNP was continued at a rate that had reduced MAP approximately 20% while phenylephrine was added in a dose sufficient to restore MAP to preinfusion levels. Patients within each group were randomized to maintenance of PaCO2 approximately 40 mmHg (groups 1a and 2a), uncorrected for body temperature, or to maintenance of PaCO2 approximately 50 mmHg (groups 1b and 2b). The following variables were maintained within a narrow range: nasopharyngeal temperature (26-29 degrees C), pump oxygenator flow (1.7-2.5 l.min-1.m-2), PaO2 (150-300 mmHg), and Hct (22-28 vol%). In each patient, controlled variables varied no more than +/- 5% between measurements. In group 1a (PaCO2 approximately 40 mmHg), MAP was 86 +/- 9 mmHg (mean +/- SD) before and 65 +/- 8 mmHg during SNP infusion (P less than 0.0001). CBF was 12 +/- 3 ml.100g-1.min-1 before and 10 +/- 2 ml.100(-1).min-1 during SNP infusion (P less than 0.01). In group 1b (PaCO2 approximately 55 mmHg), MAP was 86 +/- 11 mmHg before and 66 +/- 13 mmHg during SNP infusion (P less than 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia

Cerebral blood flow decreases with time whereas cerebral oxygen consumption remains stable during hypothermic cardiopulmonary bypass in humans.

Recent investigations demonstrate that cerebral blood flow (CBF) progressively declines during hypothermic, nonpulsatile cardiopulmonary bypass (CPB). If CBF declines because of brain cooling, the cerebral metabolic rate for oxygen (CMRO2) should decline in parallel with the reduction in CBF. Therefore we studied the response of CBF, the cerebral arteriovenous oxygen content difference (A-VDcereO2) and CMRO2 as a function of the duration of CPB in humans. To do this, we compared the cerebrovascular response to changes in the PaCO2. Because sequential CBF measurements using xenon 133 (133Xe) clearance must be separated by 15-25 min, we hypothesized that a time-dependent decline in CBF would accentuate the CBF reduction caused by a decrease in PaCO2, but would blunt the CBF increase associated with a rise in PaCO2. We measured CBF in 25 patients and calculated the cerebral arteriovenous oxygen content difference using radial arterial and jugular venous bulb blood samples. Patients were randomly assigned to management within either a lower (32-48 mm Hg) or higher (50-71 mm Hg) range of PaCO2 uncorrected for temperature. Each patient underwent two randomly ordered sets of measurements, one at a lower PaCO2 and the other at a higher PaCO2 within the respective ranges. Cerebrovascular responsiveness to changes in PaCO2 was calculated as specific reactivity (SR), the change in CBF divided by the change in PaCO2, expressed in mL.100 g-1.min-1.mm Hg-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance

Neurotrophic activities of normal and motor neurone disease patient skeletal muscle extract on cultured rat spinal neurones.

Cultured foetal rat spinal neurones, grown in serum-free medium from day 3, respond to neuronotrophic factors present in adult human skeletal muscle extracts. Levels of total protein, neurofilament protein and choline acetyltransferase (ChAT) activity are all increased approx. 2 to 3-fold at 200 micrograms extract/ml medium. Culture survival is also extended from an average of 21 days to more than 30 days. Extracts prepared from skeletal muscle biopsies of motor neurone disease (MND) patients do not differ significantly from non-MND patient muscle extracts in their ability to boost the parameter levels or survival of the cultures. The results show no evidence that neuronotrophic factors are lacking in the skeletal muscle of MND patients.

Animals

Hypercarbia depresses cerebral oxygen consumption during cardiopulmonary bypass.

No human studies have systematically examined the relations among PaCO2, cerebral blood flow, and the cerebral metabolic rate for oxygen during hypothermic cardiopulmonary bypass. We varied PaCO2 during hypothermic (26-28 degrees C) cardiopulmonary bypass and estimated the cerebral metabolic rate for oxygen by multiplying cerebral blood flow (measured using xenon-133 clearance) by the cerebral arteriovenous difference in oxygen contents. Patients were randomly assigned to either of two methods of managing PaCO2 (uncorrected for body temperature). In group 1 (PACO2 32-48 mm Hg, n = 13) the mean +/- SD cerebral metabolic rate for oxygen was 0.40 +/- 0.11 ml O2 X 100 g-1 X min-1 at a mean +/- SD PaCO2 of 36 +/- 2.0 mm Hg and 0.40 +/- 0.14 ml O2 X 100 g-1 X min-1 at a mean +/- SD PaCO2 of 45 +/- 2 mm Hg. and 49-72 mm Hg, n = 12) the mean +/- SD cerebral metabolic rate for oxygen was 0.31 +/- 0.09 ml O2 X 100 g-1 X min-1 at a mean +/- SD PaCO2 of 55 +/- 3 mm Hg and 0.21 +/- 0.07 ml O2 X 100 g-1 X min-1 at a mean +/- SD PaCO2 of 68 +/- 2 mm Hg. Group 2 values differed significantly from those in Group 1 (p less than 0.05). In both groups, cerebral blood flow increased as PaCO2 increased. During cardiopulmonary bypass, increasing PaCO2 increases cerebral blood flow and decreases the cerebral metabolic rate for oxygen.

Arteries

Baseline activated coagulation time should be measured after surgical incision.

The activated coagulation time (ACT) is widely used to guide heparin and protamine dosing during cardiac surgery. A common protocol involves establishing a baseline ACT before administering heparin, then using this ACT as a target value for assessing the adequacy of heparin neutralization after cardiopulmonary bypass. Results vary in previous comparisons of baseline ACT to postprotamine ACT, with some showing postprotamine ACT significantly below baseline values. The present study examined ACTs at three possible baseline intervals in 68 patients at two institutions: (a) before anesthetic induction; (b) after anesthetic induction; and (c) after sternotomy. Baseline ACT decreased significantly with anesthesia and surgery. The poststernotomy baseline ACT best matched the postprotamine ACT. It appears likely that surgery induces a thromboplastic response that decreases ACT. Establishing baseline ACT before anesthetic induction would predispose to false diagnoses of adequate protamine neutralization after cardiopulmonary bypass, because ACT is relatively insensitive to low concentrations of unneutralized heparin. Baseline ACTs should therefore be measured after surgical incision.

Aged

Regional cerebrovascular reactivity to carbon dioxide during cardiopulmonary bypass in patients with cerebrovascular disease.

In patients with cerebrovascular disease, hypercarbia may cause redistribution of regional cerebral blood flow from marginally perfused to well-perfused regions (intracerebral steal), as evidenced by regional cerebral blood flow studies during carotid endarterectomy. During hypothermic cardiopulmonary bypass, the pH-stat method of acid-base management produces relative hypercarbia. To determine whether pH-stat management produces relative hypercarbia. To determine whether pH-stat management induces intracerebral steals, we investigated nine patients with cerebrovascular disease undergoing coronary artery bypass grafting. During hypothermic cardiopulmonary bypass, arterial carbon dioxide tension was varied in random order between 40 mm Hg and 60 mm Hg (uncorrected for body temperature). Regional cerebral blood flow was measured by clearance of 133 xenon injected into the arterial inflow cannula. Nasopharyngeal temperature (26.8 degrees-28.0 degrees +/- 2.2 degrees-3.0 degrees C), perfusion flow rate (2.14-2.18 +/- 0.70-0.73 L/min/m2), mean arterial pressure (67-68 +/- 6-9 mm Hg), arterial carbon dioxide tension (302-308 +/- 109-113 mm Hg), and hematocrit (23% +/- 4%) were maintained within narrow limits in each patient during arterial carbon dioxide tension manipulation. Global mean cerebral blood flow values were similar to previously reported values in patients free of cerebrovascular disease; patients in this study averaged 15.2 +/- 2.5 ml/100 gm/min at an arterial carbon dioxide tension of 46.1 +/- 8.4 mm Hg and 25.3 +/- 6.1 ml/100 gm/min at an arterial carbon dioxide tension of 71.1 +/- 11.8 mm Hg. Carbon dioxide reactivity, defined as mean global cerebral blood flow (in ml/100 gm/min) divided by arterial carbon dioxide tension (in mm Hg), was similar in the region having the lowest regional cerebral blood flow and in the brain as a whole. No patient developed evidence of an intracerebral steal at the higher arterial carbon dioxide tension. During hypothermic cardiopulmonary bypass, higher levels of arterial carbon dioxide tension, such as those associated with the pH-stat management technique, are apparently not associated with potentially harmful redistribution of cerebral blood flow in patients with cerebrovascular disease.

Adult

Heparin dosing and monitoring for cardiopulmonary bypass. A comparison of techniques with measurement of subclinical plasma coagulation.

Subclinical plasma coagulation during cardiopulmonary bypass has been associated with marked platelet and clotting factor consumption in monkeys. To better define subclinical coagulation in man, we measured plasma fibrinopeptide A concentrations before, during, and after cardiopulmonary bypass. Patients were assigned to one of three groups of heparin management: group 1 (n = 10)--initial heparin dose 300 IU/kg, with supplemental heparin if the activated coagulation time fell below 400 seconds; group 2 (n = 6)--initial heparin dose 250 IU/kg, with supplemental heparin if activated coagulation time was less than 400 seconds; and group 3 (n = 5)--initial heparin dose 350 to 400 IU/kg, with supplemental heparin if whole blood heparin concentration was less than or equal to 4.1 IU/ml. Activated coagulation time and heparin concentration were measured every 30 minutes during cardiopulmonary bypass, and fibrinopeptide A was measured at hypothermia, normothermia, and whenever activated coagulation time was less than 400 seconds. Quantitative and qualitative blood clotting competence was assessed after cardiopulmonary bypass, including mediastinal drainage for the first 24 hours. Fibrinopeptide A values were markedly elevated during cardiopulmonary bypass but were well below the levels present before and after cardiopulmonary bypass. Fibrinopeptide A correlated inversely with heparin concentration during cardiopulmonary bypass (r = -0.46, p = 0.03), but higher fibrinopeptide A levels during cardiopulmonary bypass did not correlate with post-cardiopulmonary bypass coagulopathy. Group 3 patients received the highest heparin doses (p less than 0.05) and had the greatest postoperative blood loss (p less than 0.05). Protamine dose and heparin concentration during cardiopulmonary bypass correlated best with postoperative mediastinal drainage. Our findings support the following conclusions: (1) compensated subclinical plasma coagulation activity occurs during cardiopulmonary bypass despite activated coagulation time greater than 400 seconds or heparin concentration greater than or equal to 4.1 IU/ml; (2) post-cardiopulmonary bypass mediastinal drainage correlates strongly with increased heparin concentration during cardiopulmonary bypass (p less than 0.05) and protamine dose (p less than 0.05); and (3) during cardiopulmonary bypass at both normothermia and hypothermia, activated coagulation times greater than 350 seconds result in acceptable fibrinopeptide A levels and post-cardiopulmonary bypass blood clotting.

Blood Coagulation

Intraoperative use of dual-chamber demand pacemakers for open heart operations.

The availability of external atrioventricular sequential pacemakers has improved the management of patients with sinus bradycardia, junctional rhythm, and atrioventricular block. However, these pacemakers are of less value in patients with postoperative heart block and accelerated atrial rhythms. The temporary use of a modified explanted dual-chamber demand pacemaker may counteract that problem by providing atrially triggered, P-wave-synchronous ventricular pacing. We report 2 patients in whom the temporary use of the dual-chamber demand pacemaker greatly facilitated weaning from cardiopulmonary bypass after coronary artery bypass grafting.

Adult