PubMed HealthSearch

Biomedical subjects

M F James

Publications and source records attributed to M F James.

At least 19 recordsLinked to original sources

Eltanolone (5-beta-pregnanolone) does not trigger, and attenuates halothane triggering of, malignant hyperthermia in malignant hyperthermia susceptible swine.

Eltanolone is the lipid emulsion formulation, for intravenous use, of the steroid anaesthetic 5-beta-pregnanolone. We have screened this agent in malignant hyperthermia susceptible (MHS) Landrace swine to assess its potential to trigger the Malignant Hyperthermia (MH) syndrome in MHS subjects or to influence halothane triggering of MH in such patients. Administered in anaesthetic concentration, eltanolone did not trigger the MH syndrome in MHS swine. When co-administered in low dosage with halothane, the drug prevented initiation of the MH syndrome in four of eight pigs and attenuated its progress in the remainder.

Anesthetics, Inhalation

Elastogenesis in the developing chick lung is transcriptionally regulated.

The overall goals of this study were to establish the level at which elastin gene expression is regulated during chick lung embryogenesis and to identify the temporal and spatial relationships among elastogenesis, smooth muscle cell differentiation, and cell proliferation. A comparison of lung elastin mRNA and transcriptional levels during embryogenesis shows that elastin expression is developmentally regulated at the transcriptional level. The increase in elastogenic activity occurs during the late stages of lung embryogenesis and coincides with terminal maturation of the tertiary bronchi. In situ hybridization analysis demonstrates that the increase in elastin mRNA expression is confined to the tertiary bronchial respiratory subunits, connective tissue septa, and supporting vasculature of the lung parenchyma. Immunohistochemical localization of smooth muscle cell alpha-actin and tropoelastin suggests that alpha-actin-immunoreactive cells of the lung parenchyma are a major contributor to the increase in elastin expression during embryogenesis. This observation is also reflected by Northern blot analysis, which demonstrates a temporal coincidence in the increase of both alpha-actin and elastin mRNA levels. Histone mRNA expression, which was used as an index of cellular proliferation, reveals a level and spatial pattern inversely related to that of the elastin transcript. Tissue transfections of chick lungs isolated from 18-day embryos with various elastin gene deletion/reporter constructs illustrate that the elastin promoter is not promiscuous within a tissue environment and that sequences spanning the -500 to +2 region are capable of directing promoter activity spatially comparable to the endogenous elastin gene.

Actins

In vivo investigation into the effects of haemodilution with hydroxyethyl starch (200/0.5) and normal saline on coagulation.

We have investigated the effects of haemodilution with either saline or hydroxyethyl starch (200/0.5) (HES) on blood coagulation in healthy volunteers in vivo. Standard haematological tests (packed cell volume (PCV), platelets, prothrombin time (PT), activated partial thromboplastin time (aPTT), fibrinogen, antithrombin III, bleeding time and platelet aggregation), and thrombelastography (TEG) were performed before and after administration of either 0.9% saline 1000 ml or HES 1000 ml i.v. over a 30-min period. Dilution of PCV and platelet concentrations as a result of volume load were 9% in the saline group and 19% in the HES group. Reductions in fibrinogen (18.6% and 28.8%) and antithrombin III (25.5% and 37.8%) were significantly greater than could be explained by haemodilution alone in both groups. Indices of platelet aggregation were significantly enhanced by saline haemodilution, but not by HES, which inhibited epinephrine-induced aggregation and prolonged bleeding time. TEG in the saline group showed significantly shortened r and k times (24% and 26%, respectively), and increased alpha angle (24%) and maximum amplitude (MA, 6%). HES haemodilution decreased MA (11%) but did not affect other TEG variables. We conclude that haemodilution of normal blood exerted a procoagulant effect, possibly by enhancement of thrombin formation. Circulating concentrations of antithrombin III were depleted more than could be explained by haemodilution alone, leading to a hypercoagulable state. This effect was offset by an antiplatelet action of HES, which was not seen with saline. The mechanism is unknown.

Antithrombin III

Patient privilege.

Explore the source record for details and available documents.

Anesthesiology

Image processing assessment of femoral osteopenia.

Visual assessment of femoral osteopenia (the radiographic presentation of osteoporosis) is unreliable. Many of the short-comings of observer grading can be overcome by digital image analysis. Our group has developed algorithms to make automatic assessment of osteopenia from clinical radiographs. Texture Analysis Models (TA) commonly used in image analysis were investigated as measures of osteopenia. Unlike densitometric methods, TA characterizes properties of the structure of the image (ie, trabecular patterns). A group of women were analyzed whose subjects ranged from those at risk of osteoporosis (n = 24) to normal (n = 40). Using an IBM PC, frame-grabber, camera, and light-box, we appraised five statistical TA algorithms for assessment of the femoral neck in standard pelvic radiographs: (1) Fractal Signature (FS) describes the image's fractal nature. (2) Auto-Correlation of unaltered and Sobel Edge Transformed images (ACSE) measures image spatial self-similarity. (3) Co-occurrence Matrices (CM) gives the joint probability of greylevels with distance/direction and describes statistical relationships of image variation. (4) Textural Spectrum (TS) neighborhood pixel relationships measure regional directional and pixel-inversion properties. (5) Eular Numbers (EN) describe texture by properties (such as connectivity) of binary images. Good reproducibility from repeated analysis of radiographs was shown using both paired t-tests and Altman-Bland's methods. We have shown a correlation between femoral neck bone mineral density (BMD-the "gold standard" of osteoporosis assessment) and textural measures for all five algorithms. Significant measures of osteopenia were: ACSE (r = 0.6, P < .001), CM (r = -0.69, P < .001), FS (r = 0.35, P < .01), TS (r = 0.52, P < .001) and EN (r = -0.39, P < .01). Relationships were also found between textural characteristics and age/weight. TA techniques characterize the radiographic changes of bone in osteoporosis. Technology based on these ideas may have a place alongside BMD measurements in the assessment of this condition.

Absorptiometry, Photon

Hepatic energy charge and adenine nucleotide status in rats anesthetized with halothane, isoflurane or enflurane.

BACKGROUND: Volatile anesthetics are known to have varying effects on hepatic oxygen supply in vivo and have been shown to depress hepatic mitochondrial respiration and so energy charge in vitro. However, the effect of halothane, isoflurane and enflurane on hepatic adenine nucleotide status in vivo has not been evaluated. METHODS: Ninety male rats were exposed to 40% oxygen (n = 22) or 40% oxygen in equipotent (1 MAC) concentrations of halothane (1%) (n = 23), isoflurane (1.4%) (n = 22) or enflurane (2%) (n = 23) for 2 hours. All animals were then administered intraperitoneal pentobarbital and anesthesia continued and laparotomy was performed. A liver biopsy was taken for determination of hepatocellular adenosine-5-triphosphate (ATP), adenosine-5-diphosphate (ADP) and adenosine-5-monophosphate (AMP) and computation of energy charge (EC) from ¿(ATP + 1/2ADP)+(ATP + ADP + AMP)¿ and total adenine nucleotides (TAN) from (ATP + ADP + AMP). After the biopsy the aorta was cannulated for blood sampling. RESULTS: Rats in each group were similar in weight, as well as acid base and blood gas status just after liver biopsy. Hepatic energy charge, ATP, ADP, AMP, and TAN levels were not different in animals receiving either halothane, isoflurane or enflurane when compared with those receiving only oxygen. CONCLUSION: One MAC of anesthesia for a period of 2 hours with the described volatile anesthetic agents did not affect adenine nucleotide status in vivo in rats.

Adenine Nucleotides

Haemodilution induces a hypercoagulable state.

It has been suggested that haemodilution with saline may increase whole blood coagulation. This study was conducted in two parts. First, we investigated the effect of in vitro dilution of blood with saline on whole blood coagulation as measured by the thrombelastogram (TEG). Blood (4 ml) was diluted with 0.9% saline 1 ml and coagulation compared with that of an undiluted control specimen obtained concurrently from the same subject. In the second part, the study was repeated using a modified gelatin colloidal solution (Haemaccel) as the diluent. The r time, k time and r + k time were decreased relative to control in both diluent groups. The alpha angles were increased compared with control in both groups while maximum amplitude was unchanged in the Haemaccel diluted group. We conclude that haemodilution per se increases the coagulability of whole blood in vitro, but that saline haemodilution has a more marked effect on final clot strength.

Blood Coagulation

Early effects of total hepatectomy on haemodynamic state and organ uptake of catecholamines in the pig.

In a previous study, we showed that plasma concentrations of catecholamines were increased during the anhepatic phase in pigs. In this study, we investigated if a constant depth of anaesthesia would prevent these changes and, if not, if the changes were caused by impaired extraction of catecholamines. We measured arterial and venous pressures, heart rate and cardiac output in 10 anaesthetized pigs. Hepatic arterial and portal venous flows were measured. Blood for measurement of catecholamines was sampled from carotid and pulmonary arteries and portal, hepatic and renal veins. After a 2-h observation period, the liver was removed and the circulation reconstituted. Measurements were made and samples obtained for another 2 h. Catecholamine concentrations increased 2-10-fold after hepatectomy. Before hepatectomy, noradrenaline was extracted by the lung (mean extraction ratio 23 (SEM 8)%) and the liver (30 (11)%); after hepatectomy, there was extraction by the kidney (24 (12)%) but extraction by the lung (29 (8)%) was unchanged. Before hepatectomy, adrenaline was extracted predominantly by the kidney (73 (5)%) and the liver (70 (6)%), with minimal extraction by the lung; after hepatectomy, extraction by the lung increased (25 (4)%) and decreased slightly in the kidney (56 (6)%). While mean arterial pressure did not change, heart rate increased by approximately 50% and cardiac index declined (ns) within 2 h after hepatectomy. There was a sharp increase in pulmonary vascular resistance after removal of the liver and changes correlated with increases in arterial plasma concentrations of catecholamines.

Anesthesia, General

Intravenous tramadol versus epidural morphine for postthoracotomy pain relief: a placebo-controlled double-blind trial.

Tramadol, an analgesic deriving only part of its effect via opioid agonist activity, might provide postoperative pain relief with minimal risk of respiratory depression. We, therefore, evaluated it for the control of postthoracotomy pain. In this randomized, double-blind study, a single intravenous (IV) bolus dose of 150 mg tramadol (Group T) was compared to epidural morphine administered as an initial 2-mg bolus and subsequent continuous infusion at a rate of 0.2 mg/h (Group M). Patients in each group could receive morphine IV from a patient-controlled analgesia (PCA) device. Pain scores, morphine consumption, arterial blood gases, and vital capacity values were recorded at regular intervals postoperatively until 8:00 AM on the first postoperative day. Both groups obtained adequate pain relief, and there were no between-group differences in pain scores or PCA morphine consumption. Pao2 was significantly higher in Group T at 2 h and Paco2 significantly higher in Group M at 4 h postoperatively. There were no other significant respiratory differences. We conclude that a single dose of 150 mg tramadol given at the end of surgery provided postoperative analgesia equivalent to that provided by this dosage regimen of epidural morphine for the initial postoperative period.

Adult

Evolution of photochemically induced focal cerebral ischemia in the rat. Magnetic resonance imaging and histology.

BACKGROUND AND PURPOSE: Magnetic resonance imaging (MRI) is increasingly used to study the pathophysiological evolution of cerebral ischemia in humans and animals. We have investigated photochemically induced (rose bengal) focal cerebral ischemia, a relatively noninvasive, reproducible model for stroke, and compared the evolution of the ischemic response in vivo and postmortem with MRI and histology, respectively. METHODS: MR images weighted for T2, diffusion, and T2* and parallel histological sections stained with cresyl fast violet (CFV) and for glial fibrillary acid protein were obtained from 34 adult male Hooded Lister rats at seven time points (3.75 to 196 hours) after bilateral ischemia induction. From CFV histology, lesion volumes and cell counts were calculated; from diffusion-weighted and T2-weighted images, apparent diffusion coefficients and lesion volumes were determined. RESULTS: Both MRI and histology revealed a well-defined lesion at 3.75 hours after irradiation and a consistent pattern of temporal evolution; lesion apparent diffusion coefficients decreased significantly by 3.75 hours, increased significantly by day 2, and correlated strikingly with the decline in lesion CFV-positive cell numbers. After day 2, astrocytes and connective tissue cells invaded the infarct. Throughout the time course, lesion volumes determined in vivo and postmortem (after shrinkage correction) agreed well. CONCLUSIONS: MRI changes quantitatively reflect histopathology, revealing reproducible primary and secondary damage characteristics noninvasively. These changes essentially replicate those reported for other animal stroke models and clinically, emphasizing the value both of MRI and the photochemically induced focal cerebral ischemia model in stroke research.

Animals