1. We have used n.m.r. spectroscopy to measure rubidium concentrations in the skeletal muscle of live intact rats. Using a 1.9 T superconducting magnet and an ear-phone coil tuned to both protons (1H) and rubidium (87Rb), it was possible to make measurements of both tissue rubidium content and water content, and from these measurements to obtain the rubidium concentration. 2. The n.m.r. estimate of rubidium concentration in muscle in vivo was found to be a constant 31% (SEM 4%) of that estimated by flame atomic absorption spectroscopy in an extract of excised muscle. This is close to the predicted theoretical n.m.r. visibility of 33%. The visibility was constant for muscle rubidium concentrations ranging between 10 and 34 mmol/l. 3. Rubidium concentration measurement by this method is unaffected by variations in sample geometry, sample volume, tissue conductivity, coil tuning and amplifier gain. 4. By using this method to measure changes in tissue rubidium concentration with time in the same animal, it should now be possible to assess the activity of ion transport systems, such as sodium- and potassium-activated adenosine triphosphatase in vivo, by measuring the rates of change of tissue rubidium concentrations during the administration of rubidium salts. 5. This method could also be used to measure the absolute concentration of any n.m.r.-visible nucleus and could be applied to man.
\n \n\n \n \nSince the discipline expanded during 1970-1990, the number of UK consultant clinical pharmacologists has fallen. This paper describes the results of a questionnaire survey of the work patterns of 53 UK consultant clinical pharmacologists, including 35 (66%) employed by universities and 13 (25%) employed by the National Health Service (NHS). The range of activities undertaken includes: teaching medical students and others the principles of clinical pharmacology and practical therapeutics; research in a wide range of pharmacological and therapeutic areas; patient care, mostly in acute and general hospital medicine and in out-patient clinics; service both locally and nationally on a wide range of committees related to drug therapy; editorial work on learned journals and preparation of written teaching materials, including journal articles, didactic textbooks, reference books, and e-learning materials. The median amount of time that a UK consultant clinical pharmacologist spends on these activities is 50 hours per week; several work more than that. The time is spent as follows: teaching 10%; research 40%; clinical work 30%; policy and administration 12%; editorial work and writing 8%. The numbers of physicians who have been newly registered with the General Medical Council as clinical pharmacologists each year has so far been undiminished, but the number of consultant posts has fallen in 1990-2010. Many trainees therefore leave the discipline when they become consultants.
\n \n\n \n \nThe amount of published literature on adverse drug reactions is overwhelming; for example, the serial publication Side Effects of Drugs Annual lists and critically discusses over 3000 references each year. As a group, pharmacotherapeutics journals publish more papers on adverse drug reactions than journals that cover other fields, but even so they publish a minority of the total number of papers, and no single journal or group of journals can be highlighted as being a frequent source of primary information. Non-specialists must therefore rely on secondary literature (reviews) and tertiary literature (critical summaries) for information. Most of the primary published literature is in the form of anecdotal reports (30%) and formal studies or randomized controlled trials (35%). The anecdotal reports vary in quality; a new serial publication devoted to this type of article would bring some of the literature together and would improve the quality of reporting. Although many of the randomized controlled trials are of good quality and large enough to reveal benefit, most are too small to provide robust information about adverse drug reactions. Systematic reviews are too few in number (only 1.25% of publications on adverse drug reactions cited in Side Effects of Drugs Annual); more are needed.
\n \n\n \n \nOBJECTIVE: To study the activity of the sodium-lithium (Na(+)-Li+) countertransport system in vivo in the erythrocytes of patients with untreated essential hypertension. DESIGN: Lithium substitutes for sodium efflux in the sodium-sodium (Na(+)-Na+) countertransport system. In essential hypertension the efflux of lithium from cells in vitro has been used as a measure of the activity of the Na(+)-Na+ countertransporter and has been shown to be increased. We administered oral lithium and used its disposition in erythrocytes to measure Na(+)-Li+ countertransporter activity in vivo. PATIENTS: Ten men with essential hypertension who had never taken any antihypertensive treatment were matched with 10 male controls for age, weight, and plasma and erythrocyte sodium and potassium concentrations. METHODS: Repeated measurements were made of plasma and intra-erythrocytic lithium concentrations during the 48h after the oral administration of 16.2 mmol lithium carbonate. Data were analysed using standard pharmacokinetic techniques. RESULTS: The rate of lithium efflux from the erythrocytes was increased in all patients with hypertension and in none of the normotensive controls. Hill plots derived from in vivo activation curves for erythrocytic Na(+)-Li+ countertransport showed that the normotensive participants had a Hill slope of 1 (SD 0.1), whereas the hypertensives had a Hill slope of 3.2 (SD 1.0). CONCLUSIONS: The activity of the Na(+)-L+ countertransport system is increased in untreated essential hypertension in vivo; this confirms in vitro findings. A new finding is that there is a change in either the stoichiometry or the co-operativity of lithium efflux via the Na(+)-L+ countertransport system, suggesting that the rate of sodium efflux may be greater than that of influx in the cells of people with hypertension.
\n \n\n \n \nAIMS: To examine how countries differ in attitudes to adverse drug reactions by examining published scientific papers. METHODS: We searched Ovid EMBASE for publications indexed by the category \"therapeutic agents\", and the subcategory \"adverse effects\", by country for 43 countries. RESULTS: We counted 1 810 202 papers world-wide regarding therapeutic agents during 14 years, of which 195 154 (10.8%) were included in the adverse effects subcategory. There were substantial differences between countries, not explained by population, economic variation, overall publication rate on therapeutic agents, or the presence of large indigenous pharmaceutical companies. CONCLUSIONS: Many local cultural factors influence the ratio of papers on adverse reactions to all drug effects, so it may be difficult to improve their recognition and reporting by international efforts.
\n \n\n \n \nAlthough citrus fruits prevent and cure scurvy, they may not always be as good for you as you thought.
\n \n\n \n \nWe have measured specific [3H]ouabain binding and ouabain sensitive 86rubidium influx in intact human lymphocytes incubated for up to 7 days in media containing different concentrations of fetal calf serum and human serum. Incubation for periods of up to 7 days with fetal calf serum and human serum produced increases in both specific [3H]ouabain binding and ouabain sensitive 86rubidium influx that were dependent on concentration and time. Neither specific [3H]ouabain binding nor ouabain sensitive 86rubidium influx was altered when dialysed serum was used, suggesting that both fetal calf serum and human serum contain a dialysable factor or factors which stimulate specific [3H]ouabain binding and ouabain sensitive 86rubidium influx in intact human lymphocytes. To further elucidate the mechanisms underlying these changes we also measured the activity of two other enzymes of the lymphocyte plasma membrane, 5'-nucleotidase and gamma-glutamyltransferase, the uptake of [3H]thymidine by the intact cells, and the effects of cycloheximide, puromycin, and anisomycin, inhibitors of protein synthesis. The activity of 5'-nucleotidase was increased after incubation of the lymphocytes in fetal calf serum for 72 h, but the activity of gamma-glutamyltransferase was not changed, suggesting some selectivity of the stimulatory effect. Measurements of [3H]thymidine uptake by the lymphocytes showed that the major part of the observed changes in specific [3H]ouabain binding and ouabain sensitive 86rubidium influx was not attributable to transformation of the lymphocytes to lymphoblasts. All three inhibitors of protein synthesis prevented the increase in specific [3H]ouabain binding due to fetal calf serum.
\n \n\n \n \n64 of 910 hospital patients taking digoxin had a ventricular rate of less than 60 beats/min. In only 6 out of 57 of those investigated further could a diagnosis of digoxin toxicity be made on clinical, electrocardiographic, and biochemical grounds. No reason for the slow heart-rate could be found in 42 patients. Excessive vagal effects of digoxin in resting subjects may cause the bradycardia found in these inpatients in the absence of digitalis toxicity. \u00a9 1978.
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