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Biomedical subjects

W J Russell

Publications and source records attributed to W J Russell.

At least 19 recordsLinked to original sources
PubMed1995

Increased expression and activity of sodium channels in alveolar type II cells of hyperoxic rats.

We investigated the cellular and molecular events associated with the increase in sodium transport across the alveolar epithelium of rats exposed to hyperoxia (85% O2 for 7 days followed by 100% O2 for 4 days). Alveolar type II (ATII) cell RNA was isolated and probed with a cDNA for one of the rat colonic epithelial sodium channel subunits (alpha rENaC). The alpha rENaC mRNA (3.7-kb transcript) increased 3-fold in ATII cell RNA isolated from rats exposed to 85% O2 for 7 days and 6-fold after 4 days of subsequent exposure to 100% O2. In situ hybridization revealed increased expression of alpha rENaC mRNA transcripts in both airway and alveolar epithelial cells of hyperoxic rats. When immunostained with a polyclonal antibody to kidney sodium channel protein, ATII cells from hyperoxic rats exhibited a significant increase in the amount of immunogenic protein present in both the plasma membrane and the cytoplasm. When patched in the whole-cell mode, ATII cells from hyperoxic rats exhibited amiloride and 5-(N-ethyl-N-isopropyl)-2',4'-amiloride (EIPA)-sensitive currents that were 100% higher compared with those obtained from air-breathing rats. Single-channel sodium currents (mean conductance of 25 pS) were seen in ATII cells patched in both the inside-out and cell-attached modes. The number and open probability of these channels increased significantly during exposure to hyperoxia. Exposure to sublethal hyperoxia up-regulated both alpha rENaC mRNA and the functional expression of sodium channels in ATII cells.

Animals↗
PubMed1995

The relationship between clinical effect and concentrations of temazepam in plasma and cerebrospinal fluid.

The clinical pharmacodynamics of temazepam were investigated in patients who received spinal anaesthesia. Total plasma and cerebrospinal fluid temazepam concentrations were measured and correlated with the clinical effects. Sedation was measured by three separate methods. None, including an aggregated score of all three measures, was correlated closely with either the plasma or the cerebrospinal fluid levels (p = 0.86 and 0.12 respectively). Anxiety was measured before and after premedication. The two scores were correlated but the change in anxiety after premedication did not correlate with either the plasma or the cerebrospinal fluid concentrations (p = 0.11 and 0.45 respectively). Short-term memory was measured before and after premedication. The decline in short-term memory ability was moderately well correlated with both the plasma and the cerebrospinal fluid levels (p = 0.0005 and 0.013 respectively). With temazepam, the variation in sedative and anxiolytic effects between subjects is explained not by differences in pharmacokinetics but rather by differences in the pharmacodynamic response. Because sedative and anxiolytic effects are poorly correlated, but the amnesic effect is well correlated with temazepam concentrations, different sites of action for these effects are suggested.

Aged↗
PubMed1995

Effects of hypoxia on MnSOD expression in mouse lung.

Mitochondrial manganese-containing SOD (MnSOD) is located at the primary site of O2 metabolism, and its expression may be regulated by changes in O2 level. We hypothesized that lung MnSOD expression and promoter activity would decrease in response to hypoxia. We tested effects of hypoxia (10% O2 at sea level for 7 days) on chloramphenicol acetyltransferase (CAT) reporter and MnSOD gene expression in transgenic mice. The transgene consisted of a 3.3-kb portion of the rat MnSOD gene 5' flanking region coupled to a CAT reporter gene. Lung MnSOD activity in male (but not female) mice decreased significantly after hypoxia exposure. The decrease in MnSOD enzymatic activity in male mice was specific. Neither total SOD nor glucose-6-phosphate dehydrogenase (G-6-PDH) activity decreased significantly in hypoxia. CAT protein expression decreased in transgenic males exposed to hypoxia, while CAT protein expression in hypoxic transgenic females remained comparable with controls. The mRNA for both the native MnSOD and the MnSOD-CAT reporter genes remained constant after hypoxia, as did CuZnSOD and G-6-PDH mRNAs.

Animals↗
PubMed1994

Phaeochromocytoma: intraoperative changes in blood pressure and plasma catecholamines.

The aim of this study was to assess the relationship between changes in plasma catecholamine concentrations and intra-arterial blood pressure (BP) measured simultaneously during resection of phaeochromocytoma (n = 14). Arterial plasma concentrations of noradrenaline (NA), adrenaline (A) and dopamine (DA) were measured by a radio-enzymatic method. Arterial NA concentrations (pmol/ml; median and Wilcoxon 95% CI) were 71.8 (46,162) before induction of anaesthesia, 113.0 (79,231) after intubation, 375.0 (285,931) during tumour handling and 32.5 (18,88) following tumour removal. Simultaneous mean BP values (mmHg; Mean +/- SEM) were 119 +/- 8, 114 +/- 7, 159 +/- 7 (p = 0.0001) and 72 +/- 6 (p < 0.0001) respectively. At the time of tumour handling there was a weak correlation between plasma NA and A combined and mean BP (r = 0.583, p = 0.029) and a stronger correlation between log plasma NA and A combined and pulse pressure (r = 0.749, p = 0.008). The very large rises in plasma catecholamine concentrations and in BP are likely to have been causally related. Individual patients maintained a constant ratio of NA to A in plasma from pre-induction to tumour handling (r = 0.916, p < 0.0001). The maintenance of a constant NA:A ratio suggests that the pattern of catecholamine synthesis and release may be a characteristic of the individual tumour.

Adolescent↗
PubMed1994

Hydrogen peroxide release by mitochondria from normal and hypoxic lungs.

Ischemia/reperfusion mechanisms contribute to lung injury after transplantation, pulmonary embolism, and resolution of atelectasis. Alveolar tissue becomes hypoxic and deprived of substrate only when both ventilation and perfusion are interrupted, a situation modeled in vivo by complete, unilateral lung collapse. Because previously hypoxic mitochondria may be an important intracellular source of superoxide and hydrogen peroxide (H2O2) during reperfusion and re-oxygenation, the authors, in this study, investigated whether mitochondrial H2O2 release changed as a result of lung hypoxia/hypoperfusion resulting from collapse. Mitochondria were isolated from hypoxic (previously collapsed) right or contralateral left rabbits' lungs and from control rabbits' lungs. Mitochondrial H2O2 release, a marker of superoxide production, was measured fluorometrically after incubation with or without 1 mmol/L cyanide and 0.1 mmol/L nicotinamide adenine dinucleotide. Mitochondrial recovery was determined by assaying succinate dehydrogenase activity in mitochondrial preparations and lung homogenates. Lung succinate dehydrogenase activity and mitochondrial recovery were comparable among groups. Calculated lung mitochondrial content did not change (control subjects: left 7.9 +/- 0.5, right 13.8 +/- 1.7; hypoxic: left 10.3 +/- 1.3, right 10.5 +/- 2.4, all mg mitochondrial protein/lung). Mitochondria released hydrogen peroxide at approximately 5.6 nmol/h/mg pro in buffer alone and 14.8 nmol/h/mg pro in buffer with cyanide and nicotinamide adenine dinucleotide. However, lung collapse and resulting hypoxia caused no change in mitochondrial number or capacity to release H2O2 in vitro. Based on these findings, it is suggested that other sources of reactive oxygen metabolites, including xanthine oxidase and activated neutrophils, contribute to the oxidant injury observed in this model.

Animals↗
PubMed1994

Manganese superoxide dismutase expression in alveolar type II epithelial cells from nonventilated and hypoperfused lungs.

Lungs that have been hypoxic and hypoperfused because of atelectasis and the resulting decrease in pulmonary arterial blood flow develop specific decreases in manganese superoxide dismutase (MnSOD) activity and are sensitive to oxidant injury during reoxygenation. Since the MnSOD protein is concentrated in mitochondria of alveolar epithelial type II cells (ATII), we hypothesized that expression of MnSOD would be decreased in these cells also as a result of hypoxia. To investigate whether regulation of MnSOD expression occurred before or after transcription, we determined whether MnSOD protein content or steady-state mRNA level changed after hypoxia as well. ATII cells were isolated by elastase digestion from lungs of adult rabbits after right lungs had been hypoxic and hypoperfused for 7 days because of unilateral atelectasis. MnSOD activity was measured by inhibition of cytochrome c reduction in the presence of 1 mM KCN, MnSOD protein content was measured on immunoblots, and MnSOD mRNA was quantified on slot blot autoradiograms. MnSOD activity was 8.4 +/- 1.9 U/mg protein in ATII cells from control lungs and 6.8 +/- 1.5 U/mg protein in ATII cells from hypoxic and hypoperfused lungs (n = 9, P = 0.037). MnSOD protein content was 5.1 +/- 1.4 micrograms/mg protein in ATII cells from control and 4.1 +/- 1.2 micrograms/mg protein in ATII cells from hypoxic and hypoperfused lungs (P = 0.021). ATII cell MnSOD mRNA/18S ribosomal RNA (ratio of arbitrary absorbance units) determined by RNA slot blots was 2.18 +/- 1.26 in ATII cells from control lungs and 2.94 +/- 0.88 in ATII cells from hypoxic lungs (n = 7, P > 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Factors influencing mortality and myocardial infarction after coronary artery bypass grafting.

Although the mortality for coronary artery bypass graft surgery has declined, some categories of patients are still recognized as being at greater risk. Because the mortality, even for most patients with risk factors, is less than 10%, evaluating this risk and any improvement arising from changing techniques requires thousands of cases. The need for these large patient numbers makes the evaluation of changes difficult. Even when other risk factors are accounted for in the mortality estimate, the patient's age remains an important factor, although there is no obvious reason why this should be so. Similarly, female sex is well recognized as a risk factor. However, the tendency for women to have a smaller body surface area and corresponding smaller arterial diameters may be the explanation. Perfusion time appears to have a strong influence on mortality after it exceeds about 90 minutes, and a similar influence on myocardial infarction also appears to be present. The increased risk of myocardial infarction with unstable angina may relate to disruption of the normal endothelial vasodilatation caused by nitric oxide.

Age Factors↗
PubMed1994

Ultrasonographic abdominal screening of atomic bomb-exposed subjects.

Abdominal ultrasonographic screening for cancer was performed in 6,001 Hiroshima and Nagasaki A-bomb exposed and comparison subjects, all members of the Adult Health Study of the Radiation Effects Research Foundation, formerly the Atomic Bomb Casualty Commission. This study yielded 20 cancers, including 7 hepatocellular, 3 gastric, 3 renal and 2 urinary bladder cancers; one cancer each of the ovary, pancreas, colon and ureter; and one cancer metastatic to the liver, whose primary was unknown. Seventeen of these 20 subjects manifested no symptoms or signs of their disease. A variety of additional tumors, unproven and probably benign, including uterine myomata, and other abnormalities were also detected. Abdominal ultrasonographic screening greatly assisted in the detection of cancers, most of which neither the patients nor their physicians were aware. In this screened fixed population sample the cancer detection rate was 0.33%, exceeding any such rates previously reported in the medical literature.

Abdominal Neoplasms↗
PubMed1993

Mortality and myocardial infarction after coronary artery surgery. A review of 12,003 patients.

OBJECTIVE: To review the results of uncomplicated coronary artery bypass graft surgery and to identify factors which influence operative mortality (OM) and postoperative myocardial infarction (PMI). DESIGN: An analysis of the outcome in patients having coronary artery bypass graft surgery for the first time from 1978 to 1990 inclusive. SETTING: The Cardiothoracic Surgery Unit at the Royal Adelaide Hospital. PARTICIPANTS: Twelve thousand and twenty-two patients had coronary artery bypass graft surgery only. Complete data were available for 12,003 patients. RESULTS: There was an overall mortality rate of 0.99% and a postoperative myocardial infarction rate of 1.34%. Older patients and women had a higher operative mortality rate. Both unstable angina and poor ventricular function increased the mortality rate. The only significant operative factor was the perfusion time. There was a more than 16-fold increase in mortality in patients who had an average bypass time (48 minutes) compared with those whose bypass time was 100 minutes or more (0.63% v. 10.3%). The PMI rate changed over the study period, and was also influenced by the presence of unstable angina and the duration of bypass: unstable angina doubled the rate from 0.86% to 1.91%, and with an average bypass time the PMI rate was 0.56% whereas with a bypass time of 100 minutes or more the rate increased to 7.7%. CONCLUSIONS: The outcome after coronary artery bypass graft surgery is strongly dependent on the perfusion time and the presence of unstable angina. Older patients and women are more likely to die during the operation.

Adult↗
PubMed1993

Plasma catecholamine levels during exposure to an environment of hyperbaric oxygen.

Plasma catecholamine levels were measured before, during and after hyperbaric oxygen therapy in nine subjects. Adrenaline levels were elevated immediately prior to hyperbaric oxygen therapy, but then fell and stabilized once treatment commenced. No significant fluctuations in plasma dopamine or noradrenaline levels were noted during the treatment period. This study does not support the premise that there is a suppression of endogenous plasma catecholamine levels during hyperbaric oxygen as has been previously reported. The observed initial increase in adrenaline can be attributed to stress/anxiety and the subsequent decline in this stress, rather than the result of the hyperbaric oxygen treatment itself.

Adult↗
PubMed1993

The determination of absorption coefficients for measurement of carboxy-hemoglobin, oxy-hemoglobin, reduced hemoglobin, and met-hemoglobin in sheep using the IL482 CO-Oximeter.

The IL482 CO-Oximeter uses four wavelengths of visible light to analyze blood samples for the relative percentages of oxy-, carboxy-, reduced, and met-hemoglobin. In the analysis, the absorption at each of the wavelengths is multiplied by a matrix of four coefficients to derive the quantities of the four hemoglobin types. The normal settings of the CO-Oximeter coefficients are those for adult human hemoglobin. However, animal blood can be measured provided that the appropriate matrix of coefficients is available. Instrumentation Laboratory has provided sets of coefficients for several animal species. The company has also published a protocol for determining coefficients for other animal species. This protocol was examined using sheep hemoglobin-A blood and found to be inaccurate. The IL482 protocol is unsatisfactory because, if the initial error is large, successive iterations to determine the coefficient matrix through revision of the estimates of residual hemoglobin types do not converge. With sheep type-A hemoglobin, the use of human coefficients for the initial estimate gave a value of 6%, whereas, by chromatography, the carboxyhemoglobin (COHb) was 0.12% (i.e., a better initial estimate would be zero). When this was done, the final COHb estimate on "as-drawn" blood was within 1% of the COHb measured independently by gas chromatography. Revision of the protocol gave a markedly better accuracy, within 2% for COHb over the whole range when tested against mixtures of CO and O2 tonometered blood.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

MnSOD protein content changes in hypoxic/hypoperfused lung tissue.

Previous studies using an in vivo rabbit model in which lung tissue hypoxia/hypoperfusion was created by unilateral lung collapse for 7 days demonstrated a decrease in MnSOD activity in previously hypoxic/hypoperfused lungs. In the present study, we determined whether tissue hypoxia/hypoperfusion decreased MnSOD protein concentration or mRNA expression in the lung as well, changes that would suggest pretranslational regulation of enzyme activity. Expression of MnSOD may be critical in determining the degree of tissue injury during re-oxygenation because the mitochondrial electron transport system produces reactive oxygen species (ROS) both during hypoxia and re-oxygenation. We purified MnSOD protein from rabbit livers to a specific activity of approximately 3,500 U/mg protein and found the amino terminal sequence nearly identical to those of the rat and human MnSOD proteins. Lung MnSOD protein content was quantitated by immunoassay, and MnSOD mRNA content was determined by slot blotting. Results from five control and six experimental rabbits, the right lungs of which had been hypoxic/hypoperfused because of collapse for 7 days, demonstrated a 32% decrease (P < 0.03) in MnSOD protein content (42 +/- 8 micrograms/mg DNA in hypoxic lungs compared with 61 +/- 3 micrograms/mg DNA in contralateral lungs) that was not due to decreased numbers of mitochondria. Lung succinate dehydrogenase activity, a mitochondrial marker, did not change in hypoxic/hypoperfused lungs. The mRNA for MnSOD did not change relative to B-actin mRNA in lungs that had been hypoxic and hypoperfused for 7 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

The Australian Incident Monitoring Study. Errors, incidents and accidents in anaesthetic practice.

Human error is a pervasive and normal part of everyday life and is of interest to the anaesthetist because errors may lead to accidents. Definitions of, and the relationships between, errors, incidents and accidents are provided as the basis to this introduction to the psychology of human error in the context of the work of the anaesthetist. Examples are drawn from the Australian Incident Monitoring Study (AIMS). An argument is put forward for the use of contemporaneous incident reporting (eliciting relevant contextual information as well as details of use to cognitive psychologists), rather than the use of accident investigation after the event (with the inherent problems of scant information, altered perception and outcome bias). A classification of errors is provided. "Active" errors may be classified into knowledge-based, rule-based, skill-based and technical errors. Different strategies are required for the prevention of each type and it may now be useful to place more emphasis in anaesthetic practice on categories to which little attention has been directed in the past. "Latent" errors make an enormous contribution to problems in anaesthesia and several categories are discussed (e.g. environment, physiological state, equipment, work practices, personnel training, social and cultural factors). An approach is provided for the prevention and management of errors, incidents and accidents which allows clinical problems to be categorized, the relative importance of various contributing factors to be established, and appropriate preventative strategies to be devised and implemented on the basis of priorities determined from the AIMS data. Accidents cannot be abolished; however, an understanding of the factors underlying them can lead to the rational direction of resources and effort to prevent them and minimise their effects.

Accident Prevention↗
PubMed1993

The Australian Incident Monitoring Study: an analysis of 2000 incident reports.

The Australian Patient Safety Foundation was formed in 1987; it was decided to set up and co-ordinate the Australian Incident Monitoring Study as a function of this Foundation; 90 hospitals and practices joined the study. Participating anaesthetists were invited to report, on an anonymous and voluntary basis, any unintended incident which reduced, or could have reduced, the safety margin for a patient. Any incident could be reported, not only those which were deemed "preventable" or were thought to involve human error. The Mark I AIMS form was developed which incorporated features and concepts from several other studies. All the incidents in this symposium were reported using this form, which contains general instructions to the reporter, key words and space for a narrative of the incident, structured sections for what happened (with subsections for circuitry incidents, circuitry involved, equipment involved, pharmacological incidents and airway incidents), why it happened (with subsections for factors contributing to the incident, factors minimising the incident and suggested corrective strategies), the type of anaesthesia and procedure, monitors in use, when and where the incident happened, the experience of the personnel involved, patient age and a classification of patient outcome. Enrollment, reporting and data-handling procedures are described. Data on patient outcome are presented; this is correlated with the stages at which the incident occurred and with the ASA status of the patients. The locations at which the incidents occurred and the types of procedures, the sets of incidents analysed in detail and a breakdown of the incidents due to drugs are also presented.(ABSTRACT TRUNCATED AT 250 WORDS)

Accidents↗
PubMed1993

The Australian Incident Monitoring Study. Which monitor? An analysis of 2000 incident reports.

The role of monitors in patients undergoing general anaesthesia was studied by analysing the first 2000 incidents reported to the Australian Incident Monitoring Study; 1256 (63%) were considered applicable to this study. In 52% of these a monitor detected the incident first; oximetry (27%) and capnography (24%) detected over half of the monitor detected incidents, the electrocardiograph 19%, blood pressure monitors 12%, a low pressure (circuit) alarm 8%, and the oxygen analyser 4%. Of the other monitors used, 5 first detected 1-2% of incidents, and the remaining 8 less than 0.5% each. The oximeter would have detected over 40% of the monitor detected incidents had its more informative modulated pulse tone always been relied upon instead of the "bleep" of the ECG. A theoretical analysis was then carried out to determine which of an array of 17 monitors would reliably have detected each incident had each monitor been used on its own and had the incident been allowed to evolve. To facilitate "scoring" of monitors, the incidents were categorized empirically into 60 clinical situations; 40% of applicable incidents were accounted for by only 5 clinical situations, 60% by 10 and nearly 80% by 20. 98% were accounted for by the 60 situations. A pulse oximeter, used on its own, would theoretically have detected 82% of applicable incidents (nearly 60% before any potential for organ damage). These figures for capnography are 55% and 43% and for oximetry and capnography combined are 88% and 65%, respectively. With the addition of blood pressure monitoring these become 93% and 65%, and of an oxygen analyser, 95 and 67%. Other monitors, including the ECG, each increase the yield by by less than 0.5%. The international monitoring recommendations and those of the Australian and New Zealand College of Anaesthetists are thoroughly vindicated by the patterns revealed in this study. The priority sequence of monitor acquisition for those with limited resources should be stethoscope, sphygmomanometer, oxygen analyser if nitrous oxide is to be used, pulse oximeter, capnograph, high pressure alarm, and, if patients are to be mechanically ventilated, a low pressure alarm (or spirometer with alarm); an ECG, a defibrillator, a spirometer and a thermometer should be available.

Accidents↗
PubMed1993

The Australian Incident Monitoring Study. The electrocardiograph: applications and limitations--an analysis of 2000 incident reports.

The first 2000 incidents reported to the Australian Incident Monitoring Study (AIMS) were analysed with respect to the role of the electrocardiograph (ECG). Of these, 138 (7%) were first detected by the ECG. Of the 1256 incidents which occurred in association with general anaesthesia (GA incidents) 48% were "human detected" and 52% "monitor detected", the ECG was ranked third and detected 121 (19%) of these monitor detected GA incidents. However over 98% of incidents first detected by the ECG were heart rate changes; they would also have been detected by a pulse meter or pulse oximeter which would have supplied additional information about the adequacy of peripheral perfusion. The ECG is a "first-line" monitor in situations with the potential for myocardial ischaemia, complex dysrhythmias or altered myocardial conduction and should be used in all critically ill patients as well as those at significant risk of these problems. The ECG frequently detects incidents involving minor physiological trespass, such as simple heart rate and rhythm changes associated with anaesthetic agents. These incidents are generally detected relatively early in their evolution. AIMS data has confirmed, however, that the ECG has such poor sensitivity for serious physiological changes such as hypoxia, hypercarbia and hypotension that it cannot even be regarded as a useful "back-up" monitor for these problems. Indeed a "normal" ECG in a dangerous situation may lead to a degree of complacency.(ABSTRACT TRUNCATED AT 250 WORDS)

Accidents↗