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Biomedical subjects

K E Pedersen

Publications and source records attributed to K E Pedersen.

At least 19 recordsLinked to original sources

Selective stimulation of jugular ganglion afferent neurons in guinea pig airways by hypertonic saline.

We evaluated the ability of hyperosmolar stimuli to activate afferent nerves in the guinea pig trachea and main bronchi and investigated the neural pathways involved. By using electrophysiological techniques, studies in vitro examined the effect of hyperosmolar solutions of sodium chloride (hypertonic saline) on guinea pig airway afferent nerve endings arising from either vagal nodose or jugular ganglia. The data reveal a differential sensitivity of airway afferent neurons to activation with hypertonic saline. Afferent fibers (both A delta and C fibers) with cell bodies located in jugular ganglia were much more sensitive to stimulation with hypertonic saline, compared with afferent neurons with cell bodies located in nodose ganglia. Additional studies in vivo demonstrated that inhalation of aerosols of hypertonic saline induced plasma extravasation in guinea pig trachea that was mediated via tachykinin NK1 receptors. Identification of a differential sensitivity of guinea pig airway afferent nerves to hypertonic saline leads to the speculation that airway responses to hyperosmolar stimuli may result from activation of afferent neurons originating predominantly from the jugular ganglion.

Administration, Inhalation

Cysteinyl leukotrienes induce P-selectin expression in human endothelial cells via a non-CysLT1 receptor-mediated mechanism.

Cysteinyl leukotrienes are bioactive lipid mediators known to possess potent proinflammatory actions. Included in these are effects on vascular endothelium to promote surface expression of the adhesion molecule P-selectin. In the present study we were interested in investigating the receptor mechanism(s) involved in cysteinyl leukotriene-induced endothelial P-selectin expression. As such we examined the effect of several potent and selective cysteinyl leukotriene receptor antagonists on this response. Incubation of cultured human umbilical vein endothelial cells (HUVEC) with the cysteinyl leukotrienes leukotriene C4 (LTC4) or leukotriene D4 (LTD4) induced surface expression of P-selectin which was concentration dependent and rapid in onset. Expression of endothelial P-selectin induced by either LTC4 or LTD4 was not blocked however by pretreatment of HUVEC with the selective cysteinyl leukotriene-1 (CysLT1) receptor antagonists SKF 104353, pranlukast or zafirlukast before agonist exposure. In contrast, SKF 104353 effectively antagonized the LTC4-induced contractions in isolated human bronchial smooth muscle preparations, shifting the agonist dose-response curve to the right by some 3 log-fold in this tissue. The present results suggest that cysteinyl leukotrienes induce surface expression of endothelial P-selectin via a mechanism independent of the CysLT1 receptor.

Cells, Cultured

The influence of meperidine and nitrous oxide on respiratory depression in rats.

Narcotic sedation is commonly accomplished with nitrous oxide (N2O) coadministration. Concerns regarding respiratory morbidity and mortality with drug combinations have been reported in the literature, particularly in patients not receiving supplemental oxygen (O2). The purpose of this investigation was to determine the effect of meperidine alone and in combination with N2O on respiration in laboratory rats by evaluating cardiovascular and arterial blood gas data. Fifty-four Sprague-Dawley rats were assigned to one of six groups (nine per group). Groups were allocated based upon the dosage of meperidine administered (0, 4.0, or 8.0 mg/kg intraperitoneally [i.p.]) and exposure to N2O (50% with oxygen) or O2 (100%). Following meperidine administration, animals were placed into a sealed chamber through which flowed either N2O or O2. Arterial blood was obtained, at baseline and at 15-min intervals, from a femoral artery catheter and pH, O2, CO2 (mm Hg), and oxygen saturation (%) were determined. Plasma samples were analyzed using a System 1306 pH/blood gas analyzer. Group comparisons demonstrated that: (a) N2O coadministration, in animals pretreated with meperidine, did not result in increased arterial CO2 levels, and (b) as expected, arterial O2 levels in all groups increased significantly from preexposure baseline values (P < 0.05). This investigation demonstrated that the coadministration of N2O to meperidine-sedated animals did not enhance respiratory depression.

Analgesics, Opioid

[Surgical treatment of hypertrophic obstructive cardiomyopathy. A retrospective study].

Twelve patients, three male and nine female, suffering from hypertrophic obstructive cardiomyopathy were operated during the period 1976 to 1991. Operative methods were myotomy-myectomy (Morrow-procedure), mitral valve implantation or both. During the perioperative period two patients developed conduction disturbances requiring pacemaker implantation, five patients had left bundle branch block, and one died. The NYHA class was significantly reduced postoperatively (p = 0.0002). Five of eleven patients surviving the perioperative period died postoperatively after a mean follow-up of 6.3 years. It is the authors' opinion, that operation should be considered in patients suffering from hypertrophic obstructive cardiomyopathy, who have a left ventricle outflow gradient of 50 mmHg or more, and who despite medical treatment have symptoms placing them in NYHA class III-IV.

Adult

Sodium-potassium pump activity in white blood cells from children with an increased risk of developing hypertension--The Odense Schoolchild Study.

We have measured the capacity of the sodium-potassium pump, as assessed by 86rubidium uptake and the number of [3H]-ouabain binding sites on white blood cells, in children aged 9-11 years, partly cross-sectionally and partly longitudinally after a physical training programme. Children from a hypertensive subgroup comprising the upper 5% of the blood pressure distribution and children from a randomly selected normotensive subgroup were eligible for the study. In the cross-sectional study 40 children from the hypertensive subgroup and 40 children from the normotensive subgroup were evaluated. A significant increase in 86rubidium uptake was present in boys as compared to girls. After adjustment for differences in sexual maturation the observed significant difference disappeared. Important correlates of pump activity were height, plasma glucose, and physical fitness. In the training study 10 boys from the hypertensive subgroup and 10 boys from the normotensive subgroup were also evaluated after eight months of physical training. A significant fall in 86rubidium uptake was observed. No control group was examined and probably the changes reflect some effects of sexual maturation on cation handling of cells. These results indicate a significant effect of sexual maturation in capacity of sodium-potassium pump in children.

Child

Angiotensin-converting enzyme inhibition as a therapeutic principle in Bartter's syndrome.

The effect of captopril has been investigated in four patients with Bartter's syndrome treated for 12 weeks. Baseline biochemistry showed normal serum aldosterone (mean 347 pmol.l-1) and a mean serum renin of 217 mU-l-1, and a considerable increase in serum renin during captopril treatment. Serum aldosterone decreased gradually during the study period to about half its initial value. The patients presented with a mean serum potassium of 2.5 mmol.l-1, which rose to 3.4 mmol.l-1 on captopril. Lymphocytes showed a substantial captopril-induced increase in intracellular sodium (from 15 to 22.5 mmol.l-1 on average), but no change in the potassium content. Captopril was well-tolerated. It may be an alternative to potassium-sparing diuretics for maintaining normal serum potassium levels in patients with Bartter's syndrome.

Adult

Quantitative assessment of increased airway microvascular permeability to 125I-labelled plasma fibrinogen induced by platelet activating factor and bradykinin.

1. We have used 125I-labelled fibrinogen (I-FN) in experiments monitoring plasma extravasation from vessels within guinea-pig trachea and peripheral lung tissue in response to platelet activating factor (PAF) and bradykinin (BK). Retained tissue radioactivity derived from I-FN was detected by direct measurement and by autoradiography. 2. Both PAF and BK caused concentration-dependent increases in radioactivity in trachea and peripheral lung, with PAF being approximately 1000 times more potent than BK at both sites. On a wet weight basis, mean tracheal leakage responses to PAF and BK were approximately 6 times and 2 times greater respectively than those in peripheral lung. Furthermore, in trachea, the maximal response to PAF was nearly twice that to BK, although they were approximately equiactive in peripheral lung. The dipeptidyl carboxypeptidase inhibitor, enalapril (1 mg kg-1, i.v.), increased the potency of BK by approximately 40 fold. 3. In trachea, PAF (50 ng kg-1, i.v.)-induced leakage was selectively inhibited by the PAF receptor antagonist, WEB 2086 (5-50 micrograms kg-1), while responses to BK (50 micrograms kg-1, i.v.) were selectively inhibited by the BK2 receptor antagonist NPC 349 (0.5-1 mg kg-1). Neither PAF nor BK-induced leakage were significantly altered by pretreatment with the histamine H1-receptor antagonists mepyramine (10 micrograms kg-1) or ketotifen (50 micrograms kg-1) or the leukotriene receptor antagonist SKF 104353. These data indicate that both agonists caused direct, specific receptor operated increases in tracheal vascular permeability to plasma macromolecules.The alpha/beta1-adrenoceptor agonist adrenaline (100 pgkg-1) caused modest inhibition of leakage induced by BK, but not of the leakage response to PAF.4. Peripheral airway leakage responses to both PAF and BK were also detected by light microscopic autoradiography in paraffin-embedded tissue sections. This was possible since a significant amount of extravasated I-FN was apparently precipitated and fixed in the extravascular space as 125-labelled fibrin. Autoradiograms showed that both agonists caused increases in peripheral bronchial circulation microvascular permeability to I-FN. No evidence for leakage in alveolar wall capillaries or in pulmonary blood vessels was observed. Quantitation of such autoradiographic data will allow a comprehensive evaluation of the effects of putative asthma mediators on microvascular permeability throughout the respiratory tree.

Animals

Longitudinal study of changes in speech perception between 70 and 81 years of age.

As part of a large gerontological study in Göteborg, Sweden, 376 randomly selected men and women born in 1901-1902 underwent pure-tone and speech audiometry at the age of 70 years in 1971-1972. The survivors of the 1901-1902 cohort were tested again at the ages of 75, 79 and 81 years. A second group consisting of 297 men and women born in 1906 was also tested with pure-tone and speech audiometry at the ages of 70 and 75 years. We found that the median speech discrimination scores for the 1901-1902 cohort decreased moderately with increasing age: between the ages of 70 and 81 years scores decrease 10% for men and 8% for women for the worse ear and 7 and 6% for the better ear in this group. The median speech reception threshold increased 15 dB over the 11-year period for both men and women, an increase in good agreement with the increase in the pure-tone threshold over this period. Those born in 1906 had a slightly lower discrimination score (4%) when tested at the age of 70 years compared to those born in 1901 tested at the same age. As many as half of the 81-year-old persons would have a theoretical benefit from hearing aid amplification.

Aged

Magnesium content of the human heart.

Although changes in the body's magnesium status have been linked to ischemic heart disease, sudden death and arrhythmia, there is as yet no recommended, established procedure for evaluation of magnesium homeostasis. We therefore explored the relationship between the magnesium content of the heart and that of serum, lymphocytes and skeletal muscle in 50 men undergoing cardiac surgery, using biopsies from the right auricula, right atrium and skeletal muscle and simultaneously drawn venous blood for measurement of lymphocyte and serum electrolyte concentration. Median magnesium values (mumol/g wet weight) were 7.42 (3.98-8.89) in skeletal muscle, 5.49 (3.44-7.66) in right auricula and 5.80 (2.60-7.53) in right atrium. The magnesium concentration in skeletal muscle was found to correlate with that in right auricula (r = 0.46, p less than 0.01) and right atrium (r = 0.43, p less than 0.01), whereas values in serum and lymphocytes showed no correlation with the heart's magnesium content. When myocardial biopsy is not available, skeletal muscle magnesium concentration seems to be the best predictor of the human myocardium's magnesium status.

Chlorides

[Percutaneous transluminal coronary angioplasty in acute myocardial infarction].

The attitude towards the treatment of acute myocardial infarction is currently changing. As an example of one of the new methods, a successful case of acute percutaneous transluminal coronary angioplasty is presented. Which of the new therapeutic regimens provides the best prognosis is unknown, but considering the resources and the hitherto published studies, intravenous thrombolysis seems in general to be the most advantageous, while the others ought only to be used on special indications.

Adult

PAF receptors in guinea-pig and human lung.

The autoradiographic distribution and density of specific binding sites for the PAF receptor antagonist [3H]-WEB 2086 was assessed in non-diseased and asthmatic human lung and in guinea-pig airway tissue. In general, only very low levels of specific binding were detected in these tissues with no evidence for PAF receptors in airway smooth muscle. Asthma does not appear to involve significantly increased airway PAF receptor expression.

Animals

Sodium content and sodium efflux of mononuclear leucocytes from young subjects at increased risk of developing essential hypertension.

Mononuclear leucocytes were used as a cellular model for the in vitro measurements of volume, sodium and potassium content, sodium efflux rate constants and absolute sodium efflux in order to assess any cellular changes in young men at increased risk of developing essential hypertension, and to analyze whether any such changes were associated with borderline hypertension and/or heredity. Four groups of subjects were evaluated: 28 normotensive (NTO) and 20 borderline hypertensive (BHO) offspring of hypertensives, 12 borderline hypertensives with normotensive parents (BH) and 28 normotensive subjects with normotensive parents (NT). The cellular sodium/potassium contents of the four groups were not discernibly different. Ouabain insensitive sodium efflux rate constant and corresponding absolute efflux were significantly increased in offspring of hypertensives. Ouabain sensitive absolute sodium efflux was significantly increased in borderline hypertensives (BHO + BH) compared to normotensives (NT + NTO). These results indicate that leucocytes from subjects predisposed to hypertension possess an increased ouabain insensitive sodium transport mechanism and in subjects with borderline hypertension the sodium-potassium pump seems activated.

Adolescent

Increased 22Na+-influx in lymphocytes from offspring of essential hypertensive patients.

Lymphocytes were used as a cellular model for the in vitro measurements of 22Na+-influx during sodium pump inhibition by ouabain. The measurements were made using lymphocytes from young men at increased risk of developing essential hypertension in order to assess any changes and to analyse whether any such changes were associated to borderline hypertension and/or heredity. Four groups were evaluated: 28 normotensive and 20 borderline hypertensive offspring of hypertensives, 12 borderline hypertensives and 28 normotensives with normotensive parents. 22Na+-influx was significantly increased in offspring of hypertensive parents especially in the normotensive offspring of hypertensive parents. The association between heredity and increased 22Na+-influx found by us in vitro may be caused by either an increased passive sodium-influx and/or an increased sodium-sodium exchange mechanism.

Adolescent

Increased number of ouabain binding sites in lymphocytes from borderline hypertensives.

Lymphocytes were used as a cellular model for the in vitro measurements of maximal ouabain binding sites in order to assess any changes in young men at increased risk of developing essential hypertension, and to analyse whether any such changes were associated to borderline hypertension and/or heredity. Four groups were evaluated; 28 normotensive (NTO) and 20 borderline hypertensive (BHO) offspring of hypertensives. Twelve borderline hypertensives (BH) and 28 normotensive subjects (NT) with normotensive parents. The number of ouabain binding sites were significantly increased in the borderline hypertensives irrespective of heredity. The borderline hypertensives were heavier than the normotensives. A stepwise multiple regression model was therefore used in order to control confoundings by body mass index (BMI) and other factors such as age, gamma glutamyl transferase, 24 h sodium excretion, serum triglyceride, and serum cholesterol, which may influence the number of ouabain binding sites. Only BMI entered the stepwise model. These results indicate the presence of an increased number of sodium-potassium pumps in lymphocytes from borderline hypertensives. This difference may be attributed to the blood pressure disease or increased body mass.

Adolescent

Lymphocytic sodium and potassium pump function in Bartter's syndrome.

Bartter's syndrome is characterized by chronic hypokalaemia, activation of the renin-angiotensin system and normal blood pressure. To investigate whether a generalized disturbance of sodium-potassium pump function might be of pathogenetic importance, lymphocytic sodium-potassium homeostasis was examined in 5 patients suffering from Bartter's syndrome. Two of the patients were treated with potassium chloride supplementation, the others were without medical treatment when studied. All were severely hypokalemic (serum potassium 2.8 +/- 0.24 mmol/l, mean +/- SEM). Lymphocyte sodium and potassium concentration (14.4 +/- 0.37 and 94.4 +/- 7.7 mmol/l, respectively), ouabain sensitive 22Na-efflux rate constant (2.68 +/- 0.25 h), and absolute ouabain sensitive efflux rate (38.16 +/- 4.2 mmol l-1 h) did not differ from matched controls. Ouabain binding capacity was 126 900 +/- 23 500 sites/cell in patients vs 50 400 +/- 17 900 in controls (p less than 0.05). In conclusion, patients with Bartter's syndrome may have an intrinsic abnormal pump function, characterized by an increased pump density and a low cation turn-over rate per pump unit.

Adult

Changes in pure-tone thresholds in individuals aged 70-81: results from a longitudinal study.

The results of audiometric evaluation of 376 randomly selected men and women, 70 years old and born in 1901, are reported. The investigation is part of a large study on a gerontological population in which the original participants were tested again with pure-tone and speech audiometry at ages 75, 79 and 81. We also report audiometric results obtained at ages 70 and 75 from a second group, consisting of 297 men and women born in 1906. Hearing loss was most pronounced at higher frequencies for both sexes, and men had an average of 10 dB greater hearing loss at 8 kHz than women. The decrease in hearing threshold in men between the ages of 70 and 81 was more pronounced at 2 kHz (27 dB) than at 4 and 8 kHz (15 and 20 dB, respectively). The average hearing loss in women increased at a constant rate between the ages of 70 and 79 (15 dB), while between the ages of 79 and 81 the changes in pure-tone threshold was minimal. There were no significant differences in pure-tone thresholds for women born in 1901 when compared to those born in 1906 at the ages of 70 and 75. However, men born in 1906 had a more pronounced hearing loss at the age of 75 than those born in 1901.

Age Factors