Reversible inhibition of leucocyte sodium pumps by a serum factor in essential hypertension.
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Humans↗
Biomedical subjects
E A Taylor
Publications and source records attributed to E A Taylor.
Reversible inhibition of leucocyte sodium pumps by a circulating serum factor in essential hypertension.
To test whether leucocyte sodium pumps function abnormally in patients with essential hypertension specific tritium-ouabain binding (number of pumps) and ouabain sensitive uptake of rubidium-86 (86Rb+) (transport activity) were measured in mononuclear leucocytes from 37 untreated hypertensive patients and 85 normotensive subjects. Ouabain binding was lower and transport activity per binding site higher in the hypertensive patients before incubation (p less than 0.001), but both variables were normal after incubation for 72 hours with fetal calf serum. To determine whether a circulating inhibitor of sodium pumps was present in patients with hypertension ouabain binding and 86Rb+ uptake were measured in normal leucocytes before and after incubation for 72 hours with serum from 13 untreated hypertensive patients and 18 normotensive subjects. Ouabain binding was lower after incubation of cells with serum from hypertensive patients than after incubation with normal serum both before (p less than 0.01) and after (p less than 0.001) dialysis of the serum. The results suggest that in hypertension a circulating serum inhibitor of the sodium pump causes a chronic but reversible reduction in the number of pumps.
Adult↗
Imipenem pharmacokinetics in elective colorectal surgery.
A study of the pharmacokinetics of imipenem in 22 patients undergoing elective colorectal surgery was performed. Samples of plasma, fat, muscle and viscera were assayed at various intervals following intravenous injection of 1 g imipenem and 1 g cilastatin. The concentration of imipenem in plasma was approximately ten times that found in the tissues. The half-life was similar in plasma, muscle and fat (approximately 1 h). Visceral levels showed a slower fall (T 1/2 83 min). Plasma and tissue levels exceeded the MIC90 for all common pathogens for at least the first two hours of surgery. We conclude that imipenem is a suitable agent for antibiotic prophylaxis in colorectal surgery.
Colon↗
Childhood hyperactivity.
Severe degrees of inattentive and restless behaviour in childhood are a risk factor for later psychological disorders. They have many causes, but a pattern of severe and pervasive hyperactivity with poor concentration in the absence of affective or psychotic disorders should be recognised as a hyperkinetic syndrome. The syndrome is often associated with developmental delays in abilities such as language and motor control. Powerful short-term treatments are available, but long-term ways of promoting normal personality development need more research.
Attention Deficit Disorder with Hyperactivity↗
Effects of long-acting propranolol on blood pressure and heart rate in hypertensive Chinese.
In a double-blind, balanced and randomised study we used treadmill exercise to assess the effects of long-acting propranolol (LA propranolol) 160 or 320 mg or placebo, given once daily for 4 weeks, on heart rate (HR) and blood pressure (BP) in 15 Chinese subjects with mild primary hypertension (PHT). We used 24 h ECG monitoring to assess drug effects on HR. Another 18 patients were similarly assessed without exercise. Steady-state plasma propranolol concentrations after LA propranolol 160 and 320 mg were comparable to those after ordinary propranolol 80 and 160 mg daily measured in 11 and 12 separate patients. LA propranolol 160 and 320 mg reduced HR and BP before and during vigorous exercise. LA propranolol 160 and 320 mg reduced HR for 17.6 and 21.4 h of the day, and 320 mg significantly reduced the mean 24 h HR, and the mean maximum HR. The drug effects on BP and HR, and the average plasma propranolol levels after LA propranolol were similar to those reported in European subjects.
Adult↗
Measurement of specific [3H]-ouabain binding to different types of human leucocytes.
We have studied the specific binding of [3H]-ouabain to intact mononuclear leucocytes (82% lymphocytes) and polymorphonuclear leucocytes. In both types of cells [3H]-ouabain binding was saturable, confined to a single site of high affinity, slow to reach equilibrium, slow to reverse, temperature-dependent, competitively antagonized by potassium, and facilitated by the presence of divalent cations. The equilibrium dissociation constants were 2.4 +/- 0.7 nmol/l (polymorphs) and 2.4 +/- 0.4 nmol/l (mononuclear cells) (NS). The values of maximal specific ouabain binding, measured by Scatchard analysis of concentration vs binding curves (Bmax), were 33.9 +/- 6.0 fmol/10(6) cells (polymorphs) and 59.3 +/- 11.6 fmol/10(6) cells (mononuclear cells) (P less than 0.02). The corresponding numbers of sites per cell were 20415 +/- 3616 and 35712 +/- 6986 respectively (P less than 0.02). When the numbers of binding sites were expressed per square micron of cell surface area the difference between the two cell types was proportionately greater (83 and 186 sites per micron 2 respectively). We conclude that the [3H]-ouabain binding sites on mononuclear and polymorphonuclear leucocytes are similar in nature, but different in both number and density on the cell surface. Measurements of Bmax in mixed cell populations should therefore take account of cell type as well as cell size and number.
Binding, Competitive↗
Children who poison themselves. I. A clinical comparison with psychiatric controls.
Fifty schoolchildren, admitted as medical emergencies after poisoning themselves, were compared with 50 matched controls, resident in the same area of London, referred for psychiatric help for other reasons. The dependent measures were based upon systematically recorded clinical information in both groups. The self-poisoners showed more psychiatric symptoms and more disturbed family relationships than did the psychiatric group; they were more likely to meet criteria for depressive disorder and to come from families showing little warmth. This form of self-injury is not trivial or wholly culturally determined, and it warrants psychiatric intervention.
Adolescent↗
Children who poison themselves. II. Prediction of attendance for treatment.
The factors making for therapeutic engagement were examined in a series of 50 schoolchildren who had deliberately poisoned themselves. Of these 28 kept an appointment for psychiatric treatment: they were characterised by high levels of psychological symptoms, especially those of depression. The kind of treatment offered was not predictive, but parental attitudes and background contributed to the likelihood of returning for treatment. Psychiatric treatment, if effective, would be appropriate for many such children, and should be offered to them.
Adolescent↗
The optimum pH of renal adenosine triphosphatase in rats: influence of vanadate, noradrenaline and potassium.
In the presence of vanadate, the optimum pH of renal (Na+, K+)-ATPase in rats is reduced and lies in the range of intracellular pH. This explains the difference in optimum pH observed with ATP extracted from equine muscle. Removal of vanadate from such ATP (with noradrenaline) raises the optimum to the accepted range obtained with synthetic ATP. Changes in the sensitivity of the enzyme to potassium concentration contribute to the alterations in optimum pH. The optimum pH of Mg-ATPase is unaffected by vanadate. Since vanadate may be an intracellular regulator of (Na+, K+)-ATPase changes of optimum pH in relation to intracellular pH could well contribute to the regulation of sodium pump activity.
Adenosine Triphosphatases↗
The haemoglobin-oxygen dissociation curve: in vivo and in vitro effects of five beta-adrenoceptor antagonists and lignocaine.
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Adrenergic beta-Antagonists↗
Influence of environmental temperature and humidity on bronchial responses during assessment of selectivity of beta-adrenoceptor antagonists in man.
1 The effects of beta-adrenoceptor antagonists given intravenously in single doses were examined in a double-blind, placebo controlled study performed in six healthy volunteers. Heart rate and peak expiratory flow rate (PEFR) were measured at rest and during standardised exercise. 2 Atenolol 0.2 mg/kg, betaxolol 0.15 mg/kg, practolol 1 mg/kg and propranolol 0.2 mg/kg all reduced heart rate to a similar extent during exercise at 2 and 4 h after administration; betaxolol 0.6 mg/kg had a significantly greater effect than the other treatments at all times. Only betaxolol 0.15 and 0.6 mg/kg significantly inhibited exercise tachycardia at 24 h. 3 None of the treatments studied had any effect on PEFR at rest or during exercise. 4 A second study was performed to determine whether this lack of effect of propranolol on exercise PEFR could have been due to the warm and humid conditions prevailing during the experiment. Eight healthy men underwent a standardised exercise test under alternately 'warm and humid' and 'cool and dry' conditions before and after propranolol 0.2 mg/kg or saline placebo intravenously. 5 Propranolol treatment did not influence resting or exercise PEFR in either environment, but did reduce FEV1 immediately after exercise under the cool and dry conditions but not under the warm and humid conditions. 6 Comparison of the effects of beta-adrenoceptor antagonists on exercise heart rate and PEFR is not a reliable or sensitive method of measuring the cardioselectivity of these drugs. 7 Environmental temperature and humidity should ideally be controlled when the action of any drug on airflow resistance is being studied.
Adrenergic beta-Antagonists↗
The distribution of propranolol, pindolol and atenolol between human erythrocytes and plasma.
1 This study aimed (1) to measure the whole blood to plasma (WB:P) and red blood cell to plasma (RBC:P) concentration ratios of propranolol in healthy volunteers and two types of patients, and (2) to compare the concentration ratios of the lipophilic drug propranolol with moderately lipophilic pindolol and hydrophilic atenolol. 2 There was no significant difference between the WB:P and RBC:P ratios of propranolol concentration in healthy volunteers and neurological patients compared with hypertensive patients. The mean +/- s.d. WB:P ratios of propranolol concentration in the three groups were 0.74 +/- 0.03, 0.71 +/- 0.05, and 0.76 +/- 0.08 respectively. The mean RBC:P ratios were 0.39 +/- 0.08, 0.36 +/- 0.11, and 0.47 +/- 0.15 respectively. WB:P and RBC:P concentration ratios of propranolol were linearly correlated with the free fraction of drug in plasma. Propranolol was 90% bound in plasma. 3 The mean WB:P and RBC:P ratios of pindolol in seven volunteers were 0.69 +/- 0.08 and 0.37 +/- 0.14 respectively. Pindolol was 71.4 +/- 8.6% bound to plasma proteins. The concentration of pindolol in the RBC was linearly correlated with that unbound in plasma. 4 In four healthy volunteers, the mean WB:P concentration ratio of atenolol was 1.07 +/- 0.25 and the mean RBC:P ratio was 1.15 +/- 0.55. 5 The similarity of the RBC:free plasma drug concentration ratios for all three drugs suggests that the use of organic solvent partition coefficients for the prediction of in vivo distribution may be unreliable.
Adolescent↗
Cerebrospinal fluid concentrations of propranolol, pindolol and atenolol in man: evidence for central actions of beta-adrenoceptor antagonists.
1 Single and multiple oral dose studies of the penetration into CSF of three beta-adrenoceptor antagonists were performed in groups of patients needing lumbar puncture as part of their neurological investigation. Propranolol, pindolol and atenolol were chosen because of their differing physico-chemical properties. 2 The CSF concentration of propranolol (lipid-soluble) and pindolol (moderately lipid-soluble) was proportional to the free plasma concentration and was similar to, although generally lower than, that theoretically predicted. 3 The CSF concentrations of the poorly lipid-soluble atenolol were similar in different patients and were independent of plasma concentration. This may be due to the slow rate of diffusion of atenolol into CSF preventing the predicted concentrations being achieved.
Adrenergic beta-Antagonists↗
Anti-hypertensive therapy with propranolol during pregnancy and lactation.
A hypertensive women was treated throughout pregnancy with propranolol 40 mg daily without complication. At delivery the umbilical cord plasma concentration was similar to that in the maternal venous plasma. Milk:plasma ratios were less than 1, although a higher ratio would be predicted. Estimated daily intake of propranolol in breast milk by the infant was about 3 micrograms. There appears to be no reason to advise women receiving propranolol to avoid breast feeding.
Breast Feeding↗
Propranolol in experimentally induced stress.
The influence of beta-adrenoceptor antagonism on the effects of a single experimental stress was investigated in 12 healthy volunteers, using a double-blind protocol. A single oral dose of 80 mg propranolol reduced the stress-induced increase in heart rate and systolic blood pressure to 49.9 per cent and 8.3 per cent respectively compared to 61.0 per cent and 17.4 per cent with placebo. The rise in diastolic blood pressure was small and unaffected by beta-adrenoceptor blockade. The rise in temperature of the skin of the trunk was significantly reduced by propranolol. The self-rating of anxiety, alertness and concentration by the subjects was unaffected by propranolol.
Adult↗
Anaerobic axillary abscess.
Fifty-two patients with axillary abscesses were seen during two years. Staphylococcus aureus was isolated from 34, anaerobic bacteria from 12, and skin flora from five; in one case the pus was sterile. Seven patients with hidradenitis suppurativa had recurrent infection with abscess formation, which was bilateral in three. Anaerobes were isolated in five of these cases and skin flora alone in two. Anaerobes are secondary invaders in this condition, and histological examination shows that the primary abnormality is obstruction of pilosebaceous follicles and apocrine glands, associated with keratin plugging of the follicles. Chemotherapy offers little hope of cure, although metronidazole removes the offensive smell of the discharge. Radical surgery is usually indicated.
Abscess↗
Relationship between bronchial effects and plasma practolol concentration in man.
A double-blind, balanced and randomised study in 8 healthy volunteers examined the effects of relatively high versus low single doses of practolol on heart rate and ventilation at rest and during standardised exercise. Practolol 1 and 4 mg/kg, a typically non-selective drug propranolol 0.2 mg/kg, and placebo were given intravenously at weekly intervals. Cardiac beta-adrenoceptor blockade was measured by the reduction in exercise heart rate greater than 160 beats/min, and bronchial beta-adrenoceptor blockade by the reduction in exercise peak expiratory flow rate (PEFR) up to 4 h after each treatment. Results were assessed by analysis of co-variance. All three active treatments reduced exercise heart rate markedly, practolol 4 mg/kg causing most reduction. Exercise PEFR was significantly reduced by propranolol 0.2 mg/kg compared with both practolol 1 mg/kg and placebo at all times of measurement, and by practolol 4 mg/kg compared with practolol 1 mg/kg and placebo at most times. Mean plasma concentrations after practolol 4 mg/kg were 3.5 to 4.5 times higher than after 1 mg/kg. Practolol may lose its 'cardioselectivity' and cause airflow obstruction at relatively high plasma concentrations above about 2 microgram/ml.
Adult↗
Effect of propranolol on the ventilatory response to hypercapnia in man.
1. The effect of a single oral dose of propranolol on the ventilatory response to hypercapnia has been studied in five healthy subjects. 2. Propranolol produced a small but significant reduction in the slope of the ventilation/end-tidal PCO2 regression line. 3. Propranolol did not significantly change vital capacity or forced expiratory volume in 1 s.
Adult↗