Anaesthesia in haemodynamically compromised emergency patients: does ketamine represent the best choice of induction agent?

In rapid sequence induction of anaesthesia in the emergency setting in shocked or hypotensive patients (e.g. ruptured abdominal aortic aneurysm, polytrauma or septic shock), prior resuscitation is often suboptimal and comorbidities (particularly cardiovascular) may be extensive. The induction agents with the most favourable pharmacological properties conferring haemodynamic stability appear to be ketamine and etomidate. However, etomidate has been withdrawn from use in some countries and impairs steroidogenesis. Ketamine has been traditionally contra-indicated in the presence of brain injury, but we argue in this review that any adverse effects of the drug on intracranial pressure or cerebral blood flow are in fact attenuated or reversed by controlled ventilation, subsequent anaesthesia and the greater general haemodynamic stability conferred by the drug. Ketamine represents a very rational choice for rapid sequence induction in haemodynamically compromised patients.

A survey of 14 computed tomography scanners in Greece and 32 scanners in Italy. Examination frequencies, dose reference values, effective doses and doses to organs.

A survey of examination frequencies, dose reference values, effective doses and doses to organs involving 14 scanners from Greece and 32 scanners from Italy was carried out for the years 1999 and 2000. Examination frequencies per scanner and per year were found to be 3590 for Greece and 4520 for Italy. For the types of examinations considered, CDTI(W) and DLP measurements were taken. Also scan lengths used for the same types of examinations were monitored. For the same types of examinations effective doses were calculated by two methods, and it was found that their mean values ranged from 13.1 mSv for thoracic spine to 1.6 mSv for the brain examinations. From the data of the 14 Greek laboratories, doses to organs were calculated and it was found that the thyroid receives 50.2 +/- 19.8 mGy during a cervical spine examination while the gonads receive 17.8 +/- 6.9 mGy during a routine pelvis examination.

Patient dose, image quality and radiographic techniques for common X ray examinations in two Greek hospitals and comparison with European guidelines.

The radiographic technique factors and the quality of each radiographic image for three common examinations (chest PA, pelvis AP and lumbar spine LAT) were compared with the European criteria and entrance surface dose (ESD) was measured for each radiograph in two Greek hospitals. The measurements were carried out using calibrated LiF thermoluminescence dosemeters. The patients were selected so that their weight was close to 70 +/- 10 kg and their height to 170 +/- 10 cm. Effective dose values were calculated using a PC-based Monte Carlo program. All four X ray rooms in the survey achieved mean doses well below the European reference doses. However the mean doses in the X ray rooms differed by a factor of about 3.

Examination frequencies and patient doses from computed tomography examinations in the area of Athens, Greece.

A survey was conducted in the Athens region between the years 1996-1997, in which 33 CT scanner facilities from the 67 operating in this area participated. Examination frequencies from the 33 scanners were 187,875 per year for all types of examinations. Using published estimations for the mean effective dose for each type of examination, it was estimated that the collective dose from the above examinations was about 1,100 person-Sv, which, if projected to the total number of 152 CT scanners operating in Greece at the time of the survey, results in about 0.5 mSv per caput dose each year for the Greek population, which is probably the highest in Europe.

Studies on the inhibitory effects of analogues of dapsone on neutrophil function in-vitro.

We have compared twelve sulphone analogues of dapsone in terms of inhibition both of zymosan-mediated human neutrophil respiratory burst and inhibition of interleukin-1-stimulated neutrophil adhesion to transformed human umbilical vein endothelial cells. Overall, there was a good correlation between the respective rank orders of compound potency in the two test systems. The most effective compounds in terms of respiratory burst and adherence inhibition were the 2-nitro-4-amino-, 2-hydroxy-4-aminopropyl-, and 2-methoxy-4-aminoethyl- derivatives. In general, potency was inversely associated with lipophilicity; compounds with bulky side-chains, e.g. the 2-methyl-4-aminopentyl, 2-methyl-4-aminohexyl and the 2-hydroxymethyl-4-aminoethyl derivatives, were less potent. A 2-hydroxy-4-amino- derivative was the exception, however, with low lipophilicity and relatively low potency. All of the compounds tested showed comparable or greater inhibition in both the neutrophil-mediated assays compared with dapsone. Some of the compounds might, because of their good tissue penetration and lower toxicity than dapsone, have the potential to undergo further development.

A CD-ROM prototype of a multimedia-based interactive tool and guide, to perform quality control tests for the computed tomography scanners.

Quality control tests for CT scanners are very important for correct machine performance, and for the radiation protection of patients and medical personnel. As proliferation of CT scanners continues, the need for distributable software tools to perform quality control tests becomes evident. A multimedia tool and guide will help medical physicists and technologists to perform these tests easily and correctly. The guide can be easily accessible in CD-ROM, or networked on the Internet. The user, medical physicist or technologist, can find in the present guide the pertinent theoretical information and the procedures necessary to perform the quality control tests, with the help of texts, CT images and photographs, narration and video. The results of the tests are automatically compared with machine specifications and acceptable values set by international bodies, and are stored in a table.

Preliminary evaluation of the toxicity and efficacy of novel 2,4-diamino-5-benzylpyrimidine-sulphone derivatives using rat and human tissues in vitro.

Four novel combined dapsone and trimethoprim analogues, K-120, K-150, K-138 and DRS-506, have been compared with dapsone in their methaemoglobin forming abilities as well as their anti-inflammatory properties using rat and human tissues in vitro. All four compounds formed consistently less methaemoglobin compared with dapsone in both the rat and human microsomes. Using human microsomes from five livers, K-120 was significantly less toxic than the other analogues in three of the five livers (P < 0.01). DRS-506 and K-138 both inhibited the human neutrophil respiratory burst to a significantly greater degree compared with dapsone at 0.5 mM (P < 0.01), while K-120 and K-150 showed no significant effect at 0.5 mM. At 1 mM, DRS-506, K-120 and K-138 were more potent than dapsone (P < 0.01), although K-150 appeared to increase the neutrophil activation. All four analogues caused a significant reduction in neutrophil adhesion to human umbilical vein cells at 0.1 mM. In view of its efficacy and low toxicity, K-120 shows considerable promise for future clinical evaluation.

A Monte Carlo estimation of tissue optical properties for use in laser dosimetry.

In certain clinical situations, such as photodynamic therapy, light dosimetry should be considered. The propagation of light in tissues is influenced by fundamental or microscopic optical properties, namely absorption mu a and scattering mu s coefficients, refractive index n and anistropy factor g. These optical parameters can be determined experimentally by direct and/or indirect methods when tissue macroscopic properties, such as reflectance, transmittance or collimated transmittance from a tissue slab, are measured. The method described in this work provides graphical, and in simple cases analytical, 'inverse' solutions to determine tissue microscopic properties from measured macroscopic parameters. The graphs necessary for this inversion have been calculated and are provided. The method can be applied in either direct or indirect techniques and it does not depend on limitations introduced by assumptions and approximations when using theoretical models. It can also be applied for any tissue type, detector geometry and experimental apparatus. The accuracy of the method is very good over a wide range, unlimited in practice, of values of optical properties. Finally, the results of this work are in good agreement with theoretical and experimental results of other investigators.

Dose rate distributions around 60Co, 137Cs, 198Au, 192Ir, 241Am, 125I (models 6702 and 6711) brachytherapy sources and the nuclide 99Tcm.

Simple analytical functions derived from our point source Monte Carlo calculations on the combined attenuation and scatter factor, B exp(-mu r), for 60Co, 137Cs, 198Au, 192Ir, 241Am, 125I (models 6702 and 6711) brachytherapy sources and the nuclide 99Tcm, for water spherical geometries of radii R = 15 and 20 cm, are presented. Our results for the broadly used 60Co, 137Cs, 198Au and 192Ir brachytherapy sources can be compared directly and found in excellent agreement with the widely accepted data of Meisberger et al in the limited distance range for which the latter are valid. Our data, however, can be used with high accuracy outside this distance range. Many discrepancies observed among different data sets available in recent literature are attributable to differences in geometries used. The results for the recently introduced 241Am source are very dissimilar to those produced by any other currently used brachytherapy source. Dose rate distributions, based on the above simple functions, are proposed in accordance with the recommendations for calibration of the brachytherapy sources in terms of reference air kerma rate and were found to be in good agreement with data available in the literature. Our calculations for 125I sources (models 6702 and 6711), provided that the characteristic x-rays from titanium encapsulation are taken into account, support recent experimental and theoretical dose rate distributions indicating that currently accepted values for 125I may be overestimated.

Accurate Monte Carlo calculations of the combined attenuation and build-up factors, for energies (20-1500 keV) and distances (0-10 cm) relevant in brachytherapy.

The combined build-up and attenuation factor, B exp (-mu r), of point isotropic photon sources in a water medium has been calculated using the Monte Carlo method, for energies (20-1500 keV) and distances (1-10 cm) relevant in brachytherapy. For the transport of photons and electrons, up-to-date and self-consistent total, partial and differential cross sections were used. The influence of coherent (Rayleigh) and incoherent (Compton) scattering, as well as the effects of the source and medium geometries on the calculations, were investigated in detail and it was found that these effects can lead to significant deviations from published data, especially at low energies and/or large distances from the sources. Our results can be used for any mono- or multi-energetic photon source in the energy range 20-1500 keV with uncertainties of the order of 2-3%, and they may influence treatment planning especially in the case of organs at risk which are usually near the edge of the body.

Parathyroid hormone stimulation of mitosis in rat thymic lymphocytes is independent of cyclic AMP.

The in vitro mitotic response of rat thymic lymphocytes to hPTH(1-34), hPTH (1-38), and 8,18 Nle hPTH(1-34) exhibits a dependency upon extracellular calcium. Removal of extracellular calcium or the addition of Verapamil (5 micrograms/ml) or trifluoroperazine (10 microM) abrogated the mitotic response. Mitogenic concentrations of 8,18 Nle hPTH(1-34) increased calcium 45 uptake from 4.49 +/- 0.25 to 8.23 +/- 0.75 pMol/10(6) cells/min. The intracellular calcium concentration, measured by Quin 2 fluorescence, also increased after addition of 8,18 Nle hPTH(1-34). Parathyroid hormone-induced activation could not be demonstrated in an otherwise responsive thymocyte membrane adenylate cyclase. In intact cells mitogenic levels of 8,18 Nle hPTH(1-34) decreased intracellular cyclic AMP content. This response was blocked by both 3-isobutyl 1-methyl xanthine and trifluoroperazine, and may indicate activation of calcium-dependent phosphodiesterase. We conclude that PTH stimulates thymic lymphocyte proliferation independently of cyclic AMP, and that changes in cellular calcium homeostasis are intimately involved in the action of PTH. In all of the assays employed, the hitherto antagonistic analogue 8,18 Nle 34 Tyr bPTH(3-34)amide proved to be an agonist. We postulate that the receptor utilized for this PTH action may not exhibit classical PTH structure-activity specificities.

Biological effectiveness of low energy protons. I. Survival of Chinese hamster cells.

The biological effectiveness of monoenergetic protons was investigated with the track-segment method. Protons were accelerated by a Tandem Van de Graaff accelerator and their final energies were 3.0 and 7.4 MeV. The biological system used was Chinese hamster V-79 cells and their survival ability following proton irradiation was investigated. Cobalt-60 gamma-rays were used as reference radiation to assess proton relative biological effectiveness (RBE). Survival curves were obtained for the gamma-ray and proton irradiations, and the relation S = exp (-alpha D-beta D2) was fitted to the data and the parameters alpha and beta were determined. The RBE values, calculated on the basis of the mean inactivation dose D and other pertinent parameters, were found to be 1.7 +/- 0.1 and 2.8 +/- 0.2 for 7.4 and 3.0 MeV protons, respectively. Comparisons were made with the results published by other investigators and it was concluded that in this low energy range the biological effectiveness increases substantially with decreasing proton energy.

In vivo administration of interleukin 2 stimulates mitosis in thymus and bone marrow.

We have used short-term, high-density cultures to demonstrate that interleukin 2 (IL 2) in picomolar amounts causes entry of approximately 2% of thymocytes from 3-month-old rats into mitosis. Newborn and fetal animals show a higher response reflecting a greater proportion of cells which have been shown to express IL 2 receptors at this age. In vivo administration of nanogrammes of IL 2 or injection of rats with syngeneic spleen cells which had been stimulated in vitro with concanavalin A to release IL 2 were also shown to increase the proliferation of both thymus and bone marrow cells. This suggests that IL 2, in amounts which could be produced by peripheral lymphoid tissue during immune responses, could act to increase the turnover of lymphocytes in bone marrow and thymus.

Interleukin 2 stimulates T cell proliferation using a calcium flux.

A preparation enriched in rat interleukin 2 caused enhanced DNA synthesis in an interleukin 2-dependent mouse cytotoxic T cell line, in lectin transformed mouse splenocytes and in rat thymocytes. The enhanced proliferation due to interleukin 2 could be abrogated by chelating calcium from the culture medium or blocking calcium entry into the cells. Compounds which interfere with the function of calmodulin also inhibited proliferation. The addition of interleukin 2 to IL-2 dependent cells caused an increase in the intracellular concentration of calcium ions, as measured using Quin 2. The requirement for IL-2 by blasts and thymocytes could be replaced by calcium ionophore. The results implicate a calcium flux as an essential component of the action of interleukin 2 on its target cells.

The promotion of mitosis in cultured thymic lymphocytes by acetylcholine and catecholamines.

Thymic lymphoblasts possess beta-adrenergic, dopaminergic and nicotinic receptors. When activated by high concentrations of adrenaline, isoprenaline, dopamine and acetylcholine, magnesium-dependent events are initiated, which culminate in mitosis. These events can be blocked by testosterone. The cells also possess muscarinic and alpha-adrenergic receptors which respond to low concentrations of acetylcholine, carbamylcholine and noradrenaline. In these cases calcium-dependent, oestradiol-blockable mechanisms are triggered which eventually lead to cell division.

Some effects of parathyroidectomy on cell-mediated immune responses in the rat.

Xenografts of mouse tail skin to the rib cages of normal and sham-parathyroidectomized rats caused an increase in plasma calcium concentration and concomitant increase in bone marrow mitosis. Neither was elicited in aparathyroid rats and graft survival was prolonged in these animals. No hypercalcaemic episode was associated with the delayed hypersensitivity response induced by painting rat ears with oxazolone. Compared with the response in sham-parathyroidectomized rats, that in parathyroidectomized rats was enhanced although both responses were less than that in normal rats. Parathyroidectomy of parental donors did not affect the ability of their splenic lymphocytes to mount a graft-versus-host response in F1 hybrid recipients. When sham-operated and aparathyroid parents were sensitized with F1 hybrid lymphocytes no differences were observed in a subsequent graft-versus-host response in F1 recipients. However, when aparathyroid F1 recipients were employed a marked reduction in the graft-versus-host reaction was observed. Thus the clonal expansion of cells with specific reactivity to certain antigens in secondary lymphoid tissue, which is driven by those same specific antigens, is not affected or only moderately affected by the parathyroid status of the animal. However, the more general increase in lymphocyte numbers promoted by non-specific mitogenic lymphokines is markedly impaired in the hypocalcaemic parathyroidectomized rat. Furthermore, the parathyroid gland is essential for the development of a hypercalcaemic episode which follows antigenic challenge and causes cell proliferation in primary lymphoid tissues. This surge of mitosis could serve to replenish the depleted pools of virgin T and B lymphocytes in the secondary lymphoid tissue which occur as a result of their response to antigens.

Sodium and ouabain induce proliferation of rat thymic lymphocytes via calcium- and magnesium- dependent reactions.

When the concentrations of either calcium or of magnesium in the culture medium were increased from the normal 0.6 and 1.0 mM to 1.8 and 2.5 mM respectively mitotic activity of rat thymic lymphocytes increased. Very high (10(-4)M) ouabain concentrations abolished these mitogenic actions whilst lower (10(-7) and 10(-11)M) concentrations had no effect. However in the normal medium these lower concentrations of ouabain were themselves mitogenic. The stimulatory effect of 10(-7)M ouabain was calcium-dependent and oestradiol-blockable and that of 10(-11)M magnesium-dependent and testosterone-blockable. A 10 mM increment in extracellular sodium concentration also stimulated mitosis in these cells in a calcium-dependent manner whilst a 20 mM increment required the presence of magnesium to exert its mitogenic effect. However, when similar osmotic increments were provided by potassium and lithium salts, or sucrose no mitotic stimulation was provoked. Subtle interactions between sodium and the divalent cations are clearly involved in events which lead to mitosis and the steroids oestradiol and testosterone can somehow block these effects.

Changes in plasma levels of calcium and in bone marrow mitosis after antigenic challenge in rats and mice.

When rats or mice were immunized with sheep red blood cells, bacterial lipopolysaccharides or bovine serum albumin, a proliferative response could be detected in the bone marrow and spleen. This response was associated with a hypercalcaemic phase. Parathyroidectomy, which resulted in a protracted hypocalcaemia, prevented the development of an increase in levels of plasma calcium. This operation also prevented the rise in bone marrow proliferations following antigenic challenge, but did not ablate the normal proliferative response to antigen by cells in the spleen. Antibody production and numbers of antibody-forming cells were not significantly reduced by parathyroidectomy. These results suggest that there is a pool of antigen-insensitive cells in the bone marrow which are stimulated after antigenic challenge. It is postulated that these events were mediated by the development of a parathyroid-dependent hypercalcaemia which stimulates the cells non-specifically. These events may form part of a cellular homeostasis, replacing cells in peripheral lymphoid tissues.