Biomedical subjects
Publications and source records attributed to J Thode.
The observation that the ionised calcium concentration is higher if measured in the original serum sample than in an ultrafiltrate is examined by means of a theoretical model. It is concluded that this difference is a predictable consequence of the Donnan equilibrium and is not a result of protein interference with the calcium-specific electrode.
Transcutaneous carbon dioxide and oxygen tensions (tc-pCO2 and tc-pO2) were measured in seven healthy adult volunteers during hyperventilation in atmospheric air and during CO2 inhalation. Three skin sensors were applied to each subject: an O2 electrode, a CO2 electrode, and a combined O2-CO2 electrode, each heated to 44 degrees C. We observed close correlation between tc-pCO2 and capillary-pCO2, the relation being close to that calculated from the anaerobic temperature coefficient of pCO2 in blood. For O2, on the other hand, the relationship between transcutaneous and capillary values appeared more complex. Electrode drift during in-vivo monitoring was greater for pCO2 (up to 12%) than for pO2 (up to 7%), but generally we observed no differences in drift between the combined and the single electrodes. We conclude that tc-pCO2 measured with a single or a combined electrode reliably predicts capillary-pCO2 in healthy adults and that changes are rapidly observed. Our conclusions regarding tc-pO2 values are less definite because of uncertain interpretation of the capillary-pO2 values.
"Ionized calcium", in clinical chemistry, designates the free calcium ions which are present in the biological fluids as hydrated ions: Ca2+, 12 H2O. The calcium ion selective electrode measures differences in activity, however, values are reported not as the activity, but as the activity divided by the activity coefficient (gamma) of Ca2+ in "normal plasma". The latter is assumed to be equal to the activity coefficient (gamma) in a calibration solution of CaCl2 + NaCl with an ionic strength of 0,16 mol X kg-1. We have estimated the activity coefficient in this calibration solution to be gamma Ca2+ = 0,3040 (molal basis) or gamma Ca2+ = 0,3048 (substance concentration basis). The derivation of gamma Ca2+ is based on a convention for derivation of the activity coefficient of the chloride ion. We have used the Debye-Hückel equation extended by the Stokes-Robinson hydration theory plus the Bates-Staples-Robinson convention that the hydration number for Cl- is zero. International consensus is needed concerning the convention to be used for deriving the activity coefficient of Ca2+ in the calibration solutions and concerning the most appropriate value for gamma Ca2+ in normal plasma.
The changes in ionized calcium during dialysis and ultrafiltration with albumin containing solutions were highly dependent on the total electrolyte concentration. Protein interference on the calcium electrode could not explain the observation, which was, however, consistent with the Donnan theory. The uneven distribution of sodium ion also agreed with a Donnan membrane potential.
An effect of erythrocytes on the liquid junction potential of the junction "concentrated KCl whole blood" has previously been described, the effect being a positive bias of +1,4 mV with a high erythrocyte volume fraction (0.75). We have studied the erythrocyte effect with different concentrated salt solutions, and found a similar positive bias with KBr, KJ, KNO3, K2SO4, but a negative bias with NaCl, NaNO3, LiCl and CaCl2. The erythrocyte bias may be eliminated by mixing salts with opposite effect, e.g. KCl + NaCl (1.0 + 7.0 mol/l), KNO3 + NaNO3 (1.0 + 3.0 mol/l) KNO3 + Li-acetate (0.15 + 4.0 mol/l). The use of a mixed salt bridge solution may be advantageous for eliminating the erythrocyte bias when measuring ionic activity (e.g. Na+, K+, Ca2+) directly in whole blood.
Two nomograms are described. One is a Cartesian nomogram similar to the original McLean-Hastings nomogram but supplemented by an albumin scale and a pH scale to allow calculations in case of an abnormal albumin/globulin ratio or an abnormal pH. The other is an alignment nomogram. The underlying arithmetic equations, which are slightly different for the two nomograms are described. Both refer to 37 degrees C. Calculated and measured ionized calcium are compared for 24 specimens and it is concluded that the calculated value may be subject to a considerable bias amounting to 0.2 mmol/l in the worst cases. Nomograms size A4 and BASIC program are available on request.
We investigated the in vitro and in vivo relation between pH and ionized calcium during acute respiratory pH changes. The in vitro slope delta 1gcCa2+/delta pH determined in 20 healthy volunteers after equilibration at two different pCO2 values was -0.22 +/- 0.04 (mean +/- 2 SD) for whole blood and -0.24 +/- 0.04 (mean +/- SD) for serum. The in vivo slope delta 1gcCa2+/delta pH during acute respiratory changes in 10 healthy volunteers was -0.17 +/- 0.04 (mean +/- 2 SD) for capillary blood. A mathematical formula which describes the relation between pH and ionized calcium is presented.
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The concentration of free calcium ions (cCa2+), total calcium (ctCa) and pH was measured in 46 normal pregnancies at term. Measured with a combined Ca2+-pH electrode system in whole blood, maternal plasma cCa2+ was 1.18 +/- 0.03 mmol/l, and the corresponding plasma pH was 7.37 +/- 0.05 (mean +/- SD). In the cord vein, plasma cCa2+ was 1.44 +/- 0.07 mmol/l and pH 7.37 +/- 0.05. In the cord artery, plasma cCa2+ was 1.47 +/- 0.07 mmol/l and pH 7.29 +/- 0.07.
The instrument (ICA 1 Radiometer, Copenhagen) measures the activity of calcium ion and hydrogen ion and displays the estimated concentration of free calcium ion (cCa2+) and pH at 37 degrees C in 110 microliter of whole blood or serum. The cCa2+ at pH 7.40 is calculated by means of a fixed relationship between cCa2+ and pH. The results are indicated on a display approximately 1 min after sample introduction. The measuring cycle plus automatic rinsing takes 3 min. The apparatus is equipped with a number of control functions. The sensitivity of the calcium electrode showed a fall from 100% to 92% over 20 weeks. The cell potential of the calcium cell showed a slow drift of--0.02 mV per day over a 20-week period while the pH cell which employs the same reference electrode showed no drift. Interference of Na+, K+, Li+, Mg2+ and H+ on the calcium measurement in whole blood is estimated to be at most +0.1%. The effect of erythrocytes on the static liquid junction potential is minimized by a special extrapolation procedure. The analytical standard deviation for cCa2+ in serum was 0.008 mmol/l within series, 0.017 mmol/l between days. The mean value for cCa2+ (at pH 7.4) in serum for 53 healthy adults was 1.249 mmol/l with a standard deviation of 0.036 mmol/l. cCa2+ in capillary blood at the actual pH from 20 healthy volunteers gave a mean value of 1.215 +/- 0.047 mmol/l (+/- 2SD) with pH 7.428 +/- 0.031 (+/- 2 SD). The slopes delta lgcCa2+/delta pH measured after equilibration at two different PCO2 values in venous blood (n = 20) and in serum (n = 104) gave a mean value of -0.221 +/- 0.040 (+/- 2 SD). The semi-automatic combined Ca2+ - pH electrode system makes the measurement of ionized calcium for clinical use a reliable and accurate analysis.
The influence of somatostatin (a bolus injection of 250 micrograms i.v. followed by 6 micrograms/min for 40 min) on the plasma cyclic AMP, insulin, glucose and non-esterified fatty acid (NEFA) responses to i.v. adrenaline (0.07 micrograms/kg body-weight/min for 20 min) and the plasma cyclic AMP, insulin and glucose responses to a bolus injection of i.v. glucagon (0.01 mg/kg BW) were studied in normal subjects. Somatostatin suppressed the insulin response to glucagon and inhibited the insulin rebound observed on termination of adrenaline infusion. The plasma glucose response to glucagon was exaggerated by somatostatin, reflecting insulin deficiency. Neither the plasma glucose or plasma non-esterified fatty acid responses to adrenaline were influenced by somatostatin. Adrenaline produced a three-fold and glucagon a twenty-fold rise in plasma cyclic AMP and 15 min. This was not influenced by concurrent somatostatin infusion, indicating that somatostatin is not a universal inhibitor of hormone stimulated adenylate cyclase activity. This is supported by the failure of somatostatin to inhibit the metabolic actions of glucagon and adrenaline thought to be mediated by cyclic AMP.
The effect of furosemide 8 X 10(-4) mol/l an 8 X 10(-5) mol/l on parathyroid hormone stimulated adenylate cyclase was studied in renal tissue slices from guinea pigs. Furosemide caused a dose-dependent inhibition of the effect of parathyroid hormone on production of cyclic AMP, without having any significant effect on the basal cyclic AMP production. Furosemide in similar concentrations did not inhibit the stimulatory effect of thyrotrophin and fluoride in human thyroid homogenates suggesting that furosemide is not an universal inhibitor of adenylate cyclase and that the inhibition is not caused by a direct action of furosemide on the adenylate cyclase enzyme. Furosemide did not interfere with binding of cyclic AMP to cyclic AMP binding protein kinase from rabbit muscle. The results indicate that furosemide exerts an inhibitory influence either upon binding of parathyroid hormone to renal receptors or upon transmission of impulse from receptor to adenylate cyclase. The inhibitory influence of furosemide on parathyroid hormone action in kidney could explain the value of furosemide in the acute treatment of hypercalcaemia, but also suggest that chronic treatment with furosemide might interfere with normal calcium metabolism.
The effects of neurogenic block on plasma concentrations of adrenaline, noradrenaline and cyclic AMP were studied. Eighteen patients were subjected to surgery of moderate or minor extent under enflurance anesthesia with or without epidural analgesia. The results show that adrenaline secretion during surgical stress is a response to neurogenic stimuli, since the increase found in patients subjected to hysterectomy under general anesthesia is blocked by the addition of epidural analgesia. Furthermore, plasma adrenaline after neurogenic block is comparable with adrenaline levels during minor surgical stress. The plasma noradrenaline concentration does not correlate with the extent of trauma. In contrast to adrenaline levels, noradrenaline concentrations varied insignificantly during and after surgery. However, the addition of epidural block induced a postoperative increase in noradrenaline apparently unrelated to changes in heart rate or blood pressure. Simultaneous measurements of the catecholamines and cyclic AMP indicate that adrenaline is of minor importance for plasma cyclic AMP in resting patients, whereas the increase in cyclic AMP elicited by surgery reflects adrenaline-stimulated beta-adrenergic activity.
The pathogenesis of the increased operative risk in elderly patients is unknown. From a theoretical point of view, a change in endocrine-metabolic response might be involved. In the present study, a battery of hormonal and metabolic variables were measured in eight young and eight elderly healthy males undergoing elective inguinal hernial repair under general anesthesia. Blood was drawn before induction of anesthesia, at skin incision, and one, two, and six hours after skin incision. The findings were: 1) Plasma cortisol increase was significantly higher in elderly than in young controls. 2) Plasma renin level was lower in old age, but renin-aldosterone and electrolyte response patterns were alike in the two groups. 3) Thyroid parameters, in terms of serum T4, serum T3, serum rT3, and T3-resin uptake, responded normally to surgery and showed no age-related differences. 4) The hyperglycemic response was not significantly influenced by age indicating unchanged glycoregulatory mechanisms also verified by determinations of plasma catecholamines, cAMP, and insulin. 5) Blood lymphocyte count was constantly lower in elderly than in young and decreased with time, but the age-related difference was not significant. 6) Blood polymorphonuclear leukocytes showed an increase of the same magnitude in both age groups, although at a significantly slower rate in the elderly. It is concluded that age affects some aspects of the initial endocrine-metabolic response to surgery.
The possible involvement of 3', 5'-cyclic AMP (cyclic AMP) in the mechanism of action of leucocyte migration inhbitory factory (LIF) was tested. LIF-treated human peripheral blood leucocytes were incubated at 37 degrees C for various times between 0 and 22 h. The concentrations of cyclic AMP in these cultures did not differ from those in controls. Furthermore, LIF did not affect the cellular release of cyclic AMP. Neither when testing purified neutrophils, which are the prime targets of LIF action, an effect of LIF was found. Cyclic AMP levels decreased with time of incubation, whether testing mononuclear cells (92 per cent lymphocytes), purified neutrophils (98 per cent), or buffy coat cells (72 per cent neutrophils; 22 per cent lymphocytes). However, a transient and as yet unexplained increase in the cyclic AMP levels of the latter mixed population of cells was manifested within 10 to 30 min of incubation.