Biomedical subjects
Publications and source records attributed to P Mills.
Forty healthy adults who underwent rapid sequence induction of anaesthesia were allocated randomly to receive either cricoid pressure or its stimulation. The anticipated increase in systolic arterial pressure and heart rate after laryngoscopy and tracheal intubation were not altered significantly by the application of cricoid pressure.
The validity of the mathematical models that attempt to describe positron emission tomography (PET) images produced with [11CH3] methionine in terms of rates of local cerebral protein synthesis has yet to be established. A major objection to current models is that the use of methionine labeled at the methyl position results in the dispersal of the label among various methyl-accepting compounds that appear in the plasma and may then enter the brain. One approach to overcoming this problem has been the use of "standard" corrections for the activity contributed to plasma by labeled plasma protein and labeled serine. In order to determine the validity of this approach, the metabolic fate of labeled methionine was studied in six dogs. After injection with either [C3H3] methionine or [14CH3] methionine arterial blood was sampled. Plasma fractions containing protein were separated by fast gel filtration, counted with standard scintillation techniques, and their radioactivity was compared with total plasma radioactivity. Plasma was also separated by high-pressure liquid chromatography into methionine, serine, and nonmethionine or serine-containing fractions. These fractions were counted, and their radioactivity was compared with total plasma radioactivity. Labeled protein appeared in plasma about 20 minutes postinjection and then increased steadily. Labeled serine also appeared and reached a peak value of 9.4 +/- 2.1% of plasma activity at 40 minutes. Of greatest interest was the appearance in later plasma samples of increasing amounts of activity contained in nonserine low molecular weight metabolites of methionine. At 40 minutes, those metabolites made up 27 +/- 6.9% of total plasma activity.(ABSTRACT TRUNCATED AT 250 WORDS)
Stimulated-echo localized spectroscopy was combined with phase- and frequency-encoding gradients to obtain "zoom" or magnified images of specific organs in situ. The technique requires neither surface coils nor an imaging coil arrangement that exclusively isolates the target organ. This technique can be readily applied to conventional spectrometer imagers that have limited computational capabilities.
The disaggregation behavior of erythrocytes in dextran saline solution was investigated by a light reflectometry technique in a Couette flow and in a plane Poiseuille flow. Dextran concentration and mass average molecular weight of the polymer fraction strongly influence the shear stress dependence of the erythrocyte suspension reflectivity in shear flow and the critical hydrodynamic conditions (shear rate or shear stress) for near-complete cell dispersion. We investigated the influence of cell volume fraction and membrane deformability (heat treatment of the erythrocytes) on the reflectivity of the flowing suspension. This study indicates that the intercell adhesiveness and the shear stress are the only parameters that influence rouleau break-up in steady uniform shear flow, thus eliminating cell volume fraction and membrane deformability as possible factors. However, the critical cross-sectional average shear stress for near-complete cell dispersion through the flow cross-section is shown to depend on the flow pattern. The rotation of cells in a shear flow or the nonuniform shear field in Poiseuille flow indeed increases the flow resistance of cell aggregates. We give a theoretical description of the shear-induced cell disaggregation process in Couette flow and in plane Poiseuille flow. The quantitation of shear forces for cell dispersion provides a way for estimating the surface adhesive energy of the bridging membranes by fluid mechanical technique.
We used 31P spectroscopy to determine whether administration of a neutralizing dose of bicarbonate in rabbits with lactic acidosis caused a paradoxical brain intracellular acidosis. Ten 10- to 16-day-old rabbits were anesthetized with 0.75% halothane/oxygen and their lungs mechanically ventilated. Metabolic acidosis was induced by decreasing PaO2 to 25 to 35 mm Hg for 1 to 2 hours until the base deficit was 10 to 15 mEq/L. Cerebral ischemia was prevented by maintaining arterial blood pressure at +/- 20% of control value with a venous infusion of epinephrine. Hypoxia was then terminated by administration of 100% oxygen, which was continued for the remainder of the study. After 15 minutes 100% oxygen, 5 mEq/kg 4.2% bicarbonate was administered to five animals; 5 minutes later the same dose was repeated. Control rabbits were given equal volumes of saline solution. In all animals, arterial pH decreased from 7.43 +/- 0.06 to 7.25 +/- 0.08 (SE) during hypoxia, and brain intracellular pH from 7.22 +/- 0.06 to 7.09 +/- 0.09 (SE). Both pH values remained low during reoxygenation. Bicarbonate administration normalized arterial pH (7.41 +/- 0.03), whereas treatment with saline solution did not (7.23 +/- 0.01, P less than 0.05). PaCO2 rapidly increased by 10 mm Hg in the bicarbonate group, and remained elevated; it was unaffected by saline solution administration. Brain intracellular pH in the bicarbonate group increased by 0.12 U over 40 minutes, but intracellular pH in the saline solution group decreased 0.05 pH U (P less than 0.05) over the same period. We conclude that administering a total dose of 10 mEq/kg sodium bicarbonate to neonatal rabbits recovering from hypoxic lactic acidosis increases arterial pH, brain intracellular pH, and PaCO2; it does not produce paradoxical intracellular acidosis in the brain.
A recent NMR study reported the elimination of halothane from the brain of rabbits to be ten times slower than expected, based on known anesthetic solubility and cerebral blood flow. The authors conducted a study in five rats using fluorine nuclear magnetic resonance (NMR) spectroscopy to see if major pharmacokinetic discrepancies are associated with the uptake, maintenance, and elimination of halothane from the brain. The rats underwent a 60-min period of halothane anesthesia. They employed a spatially selective NMR spectroscopy technique known as surface coil "depth-pulsing" to assure that the fluorine NMR signals originated in brain tissue, and not in the scalp, muscle, adipose tissue, and bone marrow that surround the brain. After the inspired anesthetic concentration was decreased to zero, the amplitude of the fluorine NMR signal decreased to 40% of its maximum value within 34 +/- 8.0 minutes (n = 5), rather than after 7 h as in the recent study, where the fluorine signal may have contained substantial contributions from metabolites or tissues outside the brain. Fluorine was barely detectable in all of the animals 90 min after stopping the administration of halothane. The authors' results are in agreement with model calculations and several other investigations.
19F nuclear magnetic resonance spectroscopy was performed at 2.0 Tesla to evaluate the washout of isoflurane from the adult rabbit brain after 90 min of anesthesia. This investigation reconciles previous in vivo NMR studies of others, which observed a slow anesthetic washout, with invasive non-NMR studies that found a rapid washout, as predicted by perfusion-limited models of anesthetic uptake and elimination. Two NMR surface coil experiments were performed: in the first, a 1-cm surface coil was placed directly over the exposed dura to be certain that the washout was observed only from the brain; in the second, a 3-cm coil was placed noninvasively over the intact scalp to emulate previous NMR experiments. As in previous NMR experiments, a slow washout of isoflurane was observed with the large coil. The NMR signal that is observed with the large coil cannot be attributed solely to brain tissue. Fat surrounding the brain contributes significantly to the fluorine NMR spectra that are observed with the 3-cm coil, and its contributions lengthen the apparent washout time. A rapid washout of isoflurane from the rabbit brain was observed with the small coil, whose signal unambiguously arises only from brain tissue. The observed rapid washout is consistent with previous invasive biochemical measurements of anesthetic washout from the brain.
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A slow growing encapsulated haemangioma of the left atrium was diagnosed by means of cross sectional echocardiography. The heterogeneous nature of the tumour was reflected in a central area of relative echolucency. After successful surgical removal of the tumour, the patient's symptoms of lethargy and limited exercise capacity improved considerably.
The key feature of the kinetics and equilibria of both specific and non-specific noncovalent interactions of proteins with nucleic acids is their sensitivity to the details of the ionic environment. Investigation of the effects of ion concentrations provides detailed and otherwise unobtainable information about the thermodynamics and mechanisms of these interactions. We discuss the molecular and thermodynamic basis of the contribution to these ion effects from electrolyte-nucleic acid interactions, and demonstrate that a simple ion exchange formalism, involving the stoichiometric participation of individual ions, is the appropriate basis for interpreting these profound effects at a thermodynamic level. Since the in vivo ionic environment is both complex and variable, we propose that variations in intracellular concentrations of individual ions play both global and specific roles in the control of the protein-nucleic acid interactions responsible for nucleoprotein structure and gene expression.
The aggregation behaviour of normal and heat treated (48.4 degrees C, 48.8 degrees C, 49.5 degrees C) red blood cells (RBCs) suspended in dextran-saline solutions (Dx 70, Dx 173) was investigated by a laser light reflectometric method over a wide range of bridging energies. The characteristic times of rouleau formation were found to be increased after RBC heat treatment. The disaggregation shear stress is not significantly different between normal RBCs and heat treated RBCs. The loss of cell deformability is nevertheless shown to improve slightly the dissociation efficiency of the flowing liquid in a shear flow resulting in a small reduction of the disaggregation shear rate after heat treatment. Heat treatment is also shown to alter the structure of RBC network at equilibrium. These results indicate that heat induced alterations of erythrocytes only affects the mechanical properties of the cell membrane without significant changes in the macromolecular bridging energy.
The effects of pimozide, a dopamine (DA) receptor blocker, on associative learning was examined using two appetitively motivated choice paradigms. In Experiment I, low to moderate doses of pimozide (0.125, 0.25 mg/kg) were not found to disrupt the acquisition of a two bar simultaneous discrimination task. However, with continued testing, progressive deficits in response accuracy were observed in rats pretreated with 0.25 mg/kg pimozide. When subsequently tested drug-free these animals demonstrated a rapid and marked improvement in performance. Experiment II used a spatial discrimination task (T-maze) requiring a natural response (running) with minimal response demands (short stem and arms). Rats pretreated with 0.25, 0.50, and 1.0 mg/kg pimozide showed comparable levels of acquisition and maintained discriminated performance relative to vehicle controls. Similar results were obtained when the reinforced (S+) and nonreinforced (S-) stimuli were reversed. Moreover, animals receiving 2.0 mg/kg pimozide and not rendered cataleptic also demonstrated acquisition of both the initial discrimination and its reversal. It was concluded that rats pretreated with pimozide are able to acquire the significance of environmental stimuli and direct their responding accordingly if they are motorically capable of emitting the required response.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
A Laser Doppler velocimeter (LDV) was modified in order to reduce the dimensions of the crossing section of the two light beams. This LDV has been used on plane capillary tubes (100 mu m less than or equal to inside thickness less than or equal to 400 mu m) in which different sorts of suspensions were flowing. The flow rate Q, and pressure, delta p, measurements were recorded simultaneously. The velocity profile measurements were done. We have verified that the velocity profile blunting depended on hematocrit, flow rate. Such profiles were in good agreement with theoretical ones obtained with a model where aggregation and deformation levels were described by characteristic coefficients involved in a viscosity equation.