Activation of Lyt-2+ T cells by antibodies towards brain-associated antigens. I. Accessory cell requirement and role of Fc receptors in the induction of reactivity to interleukin 2

The present report describes a system where essentially all Lyt-2+ T cells are selectively activated by rabbit anti-mouse brain antibodies (RaMB) to interleukin 2 (IL 2) reactivity. High efficiency of RaMB-mediated induction was obtained by a 5 h incubation with antibodies at high cell density of Sephadex G-10-nonadherent spleen cells. No in situ production of IL 2 by RaMB-treated cells was detected, and proliferative responses were entirely dependent on exogeneous IL 2. RaMB-induced IL 2 reactivity was found to require accessory cells which are Fc receptor positive, and clearly distinct from those required to induce T cell proliferation in mixed lymphocyte cultures. We conclude that Lyt-2+ T cells are triggered to IL 2 reactivity by Fc receptor-mediated presentation of RaMB antibodies. The mechanism of induction by RaMB antibodies is discussed.     

Enzyme-linked immunosorbent assay for immunological diagnosis of human tularemia.

The enzyme-linked immunosorbent assay (ELISA) was applied for immunological diagnosis of human tularemia, using lipopolysaccharide from Francisella tularensis as antigen. Sera collected from patients, healthy individuals, and vaccinated volunteers were investigated for antibodies against F. tularensis by ELISA and tube agglutination. In ELISA all sera were titrated with a polyspecific anti-immunoglobulin enzyme conjugate. A limited number of consecutive sera from individual patients were also investigated for immunoglobulin G (IgG) and IgM antibodies by means of immunoglobulin class-specific conjugates. On an average ELISA was more than 10-fold as sensitive as tube agglutination. Two weeks after onset of disease, sera from patients had significantly higher titers in ELISA than sera from healthy controls. High titers persisted after more than 2 years. Significant amounts of both IgG and IgM antibodies were present within 1 to 2 weeks after infection. The antibody activity increased during the first month, without any significant change of the relation between IgG and IgM titers. After 2.5 years the IgG/IgM titer ratio of sera from patients was significantly increased. Within 6 weeks after vaccination sera from about half of the vaccinees had significantly elevated titers in ELISA. Titers observed after vaccination were generally lower than those found after infection. An elevated ELISA titer can be of diagnostic importance by the end of the first week of illness. A significant increase of titer in consecutive serum samples indicates a diagnosis of tularemia. Determination of IgG and IgM antibodies may be of value in determing whether a positive titer of a single serum sample is of longstanding or recent origin.     

Damaged chromatin does not prevent the exit from metaphase I in fused mouse oocytes

The presence of checkpoint mechanisms which are able to recognize damaged chromatin and thereafter to prevent exit from metaphase I has been investigated in giant mouse oocytes produced by fusion of a normal metaphase I oocyte with an equivalent oocyte with damaged chromatin. The presence of damaged chromatin did not prevent the onset of anaphase I in both sets of chromatin in the fused cells. Interestingly, fused or unfused cells containing only damaged chromatin failed to enter anaphase and persisted instead in a metaphase-like state. These results demonstrate the fragility of checkpoint controls in mammalian female germ cells.      

The role of descending inhibition in the antinociceptive effects of the pyrazolone derivatives,metamizol (dipyrone) and aminophenazone (“Pyramidon”)

Summary The study was carried out to provide further evidence that the two pyrazolone derivatives, metamizol and aminophenazone, produce central antinociceptive effects by stimulating inhibition descending from the periaqueductal grey (PAG) to the spinal cord. Experiments were carried out on rats in which the tail-flick response to radiant heat, nociceptive activity in ascending axons of the spinal cord, and activity of neurones in the PAG and the substantia nigra were studied. Microinjection of procaine (10 g) into the PAG reduced the tail-flick latency and abolished the increase in latency caused by i.p. injection of metamizol (40 mg/kg) and aminophenazone (150 mg/kg); it did not significantly reduce the antinociceptive effect of i.p. injection of morphine (2 mg/kg). Threshold doses of morphine (1 and 2 g) administered by intrathecal (i.t.) injection potentiated the effect of threshold doses of metamizol injected i.p. (10 mg/ kg) or into the PAG (10 g) in the tail-flick test. Morphine (2 g) injected i.t. potentiated the effect of i.v. injection of metamizol (80 mg/kg) on nociceptive activity in ascending axons by eliminating the stimulant effect of metamizol on about one third of the axons. Threshold doses of morphine injected i.t. failed to potentiate the antinociceptive effect of aminophenazone (50 mg/kg) injected i.p. in the tail-flick test. The results support the view that metamizol and aminophenazone activate pathways descending from the PAG and exerting an inhibitory effect on nociceptive impulse transmission at the spinal level.Supported by the Schwerpunkt Nociception and Schmerz of the Deutsche Forschungsgemeinschaft Send offprint requests to I. Jurna at the above address     

Respiratory effects in two-dimensional Fourier transform MR imaging

Respiratory and other regular motions during two-dimensional Fourier transform magnetic resonance imaging produce image artifacts consisting of local blurring and more or less regularly spaced "ghost" images propagating along the direction of the phase-encoding magnetic field gradient. The patterns of these ghost artifacts can be understood in terms of the technique of image production and basic properties of the discrete Fourier transform. This understanding permits, without respiratory gating, production of images of improved quality in body regions in which there is significant respiratory motion. In particular, the ghosts can be maximally separated from the primary image by choosing intervals between phase-encoding gradient pulse increments that are equal to one-half the respiratory period; they can be minimally separated by choosing an interval equal to the respiratory period. Increasing the number of signal averages between each phase-encoding increment decreases the intensity of the ghosts.     

Clinical implications of continuous measurement of energy expenditure in mechanically ventilated patients

Energy expenditure was monitored in 20 critically-ill mechanically ventilated patients using the Siemens-Elema Oxygen Consumption Calculator (OCC 980). Energy expenditure was measured continuously over the 24-h period in all patients (altogether, over 2500 patient hours; range 48-288 h). A predicted energy expenditure was calculated for each patient from standard tables for basal metabolic rates modified according to previously published reports on the influence of trauma, infection and elevated body temperature. For all patients combined, the agreement between the predicted and the measured energy expenditure was good. However, in individual patients the measured energy expenditure varied between 48 and 148% of the predicted value. The measured energy expenditure in surviving traumatized and/or septic patients correlated well (95-100%) with the predicted value at the time when weaning off the ventilator could be initiated. On the first day of measurements, the energy expenditure (in % of the predicted value) in the six patients who later died was significantly lower than in surviving patients (84 +/- 6 vs 107 +/- 2%; p < 0.01). Over a 24-h period, energy expenditure, defined as the value noted during a stable 30-40-min period of measurement, varied between 12 and 50% in the individual patients. This study shows that energy expenditure cannot be accurately predicted in the individual patient, that an energy expenditure below predicted values appears to be indicative of a poor prognosis and that short periods of energy expenditure monitoring may fail to reflect 24-h conditions.     

Continuous blockade of the lumbar plexus after knee surgery: a comparison of the plasma concentrations and analgesic effect of bupivacaine 0.250% and 0.125%

In 20 patients a continuous block of the lumbar plexus was administered after knee-joint surgery, and the analgesic effect of two different concentrations of bupivacaine was compared. The same volume of bupivacaine was given to both groups of patients: a bolus dose of 0.4 ml/kg, 0.5% or 0.25%, followed by infusion of 0.14 ml/kg/h, 0.25% or 0.125%, respectively, via a catheter placed in the neurovascular fascial sheath of the femoral nerve according to the "3-in-1 block" technique. The median morphine consumption during the first 16 h postoperatively was 6.0 mg when bupivacaine 0.5/0.25% was used and 9.5 mg when 0.25/0.125% was used. This difference is not significant. The visual analogue pain scores were also similar in the two groups (P greater than 0.05). All plasma concentrations were below 4 micrograms/ml, the highest concentration measured being 3.6 micrograms/ml. It is concluded that when used for a continuous block of the lumbar plexus after knee-joint surgery, bupivacaine in a concentration of 0.125% offers the same pain relief as a concentration of 0.25%, and the risk of toxic reactions is reduced.     

The role of national quality registers in the Swedish health service

This article reports on a quality movement in Sweden that has gone largely unnoticed, namely the national quality control registers. These registers represent a potentially important primary data source for comparative studies and can play an important role in a national strategy for control and improvement of health care quality. First, we review the recent health care quality initiatives in Sweden and the background of national quality control registers. Secondly, we discuss our findings from a study on the purpose, content, value and problems associated with the registers. Our findings are based on (a) interviews with physician managers of the registers, (b) questionnaires to selected hospital departments participating in the registers and (c) questionnaires to elected officials and administrators representing the local health care providers. Finally, we discuss several crucial issues related to the registers. Although some have existed for several years, the registers are still defining their roles. Traditionally, this activity has been managed by the medical profession. However, interest in register information is increasing among health care policy makers and administrators at all levels in the system. Two key issues concern register ownership and finance, but the most sensitive issue concerns the right of policy makers and the public to access register information. The registers and the information they contain illustrate the ongoing conflict between openness and consumer sovereignty in health care on the one hand and professional autonomy on the other.     

Pharmacokinetic and pharmacodynamic responses to chronic administration of the selective serotonin reuptake inhibitor citalopram in rats

The number of drugs used to treat affective disorders such as depression is rapidly increasing. Citalopram (CIT), an antidepressant, is a selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitor (SSRI). In the present study, rats were treated with 10 mg/kg/d racemic CIT for two weeks with use of osmotic pumps, and the following were monitored: open-field behavior, racemic and enantioselective concentrations of CIT and metabolites in blood, brain parenchyma, and extracellular space, and the brain extracellular monoamine levels. The racemic CIT concentration in serum was estimated about tenfold lower than in brain parenchyma but much higher than in brain extracellular fluid. The major CIT metabolites, demethylcitalopram (DCIT) and didemethylcitalopram (DDCIT) were 20% and 30%, respectively, of the amounts of CIT in serum and even lower in the brain parenchyma. The S-enantiomer/R-enantiomer ratios for CIT and DCIT were about 1.01 and 0.31, respectively, in blood and brain. There was a clear correlation between the different drug components within and between blood and brain compartments. Citalopram had no measured effect on open-field behavior, but it elevated extracellular 5-HT and decreased 5-HIAA levels. No correlations between any of the drug components and the brain monoamines were found. In summary, the drug components after chronic dosing correlated well between the periphery and the brain, but not with the brain monoamine concentrations. Further studies investigating the combined pharmacokinetic/dynamic effects could take advantage of blood drug monitoring for the commonly used novel antidepressant drugs.