Mode of action of diuretics in cardiovascular disease.
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Biomedical subjects
Publications and source records attributed to A R Michell.
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The fate of most aspiring veterinary surgeons is determined not by their professional examinations but by their A-level results. Anything less than two As and a B and the outlook is bleak, though not irretrievable. In this article, Dr Robert Michell examines the system by which students are selected, and suggests that the system is ripe for re-evaluation.
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The severity of acid-base disturbances in diarrhoeic calves was investigated and a simple, inexpensive method of monitoring them was evaluated. The Harleco apparatus measures the 'total carbon dioxide' in a blood sample, mostly generated from the bicarbonate present, and any abnormalities are mainly due to metabolic acidosis or alkalosis. Its performance was tested against a standard blood gas analyser by comparing the results obtained by both methods with nearly 2000 blood samples from healthy or diarrhoeic calves. After technical modifications, the technique gave excellent precision and accuracy for the clinical evaluation of acid-base balance, using venous whole blood. The samples were very stable, especially at 0 degrees C, but also at room temperature. The normal range (mean +/- 1.96 sd) for total carbon dioxide in whole blood from calves was 21 to 28 mmol/litre. For samples corresponding to mild, moderate or severe acidosis, 79 per cent were correctly classified by the Harleco apparatus and only 0.1 per cent were beyond the adjacent degree of severity. After four days of diarrhoea, the calves which later died had twice the deficit in plasma bicarbonate of those which survived. As death approached, the deficit was almost three times that in surviving calves and the blood pH shortly before death was as low as 6.79 +/- 0.08. The Harleco apparatus was less successful with alkalotic samples, but metabolic alkalosis is less common and usually less severe.
Five commercially available parenteral solutions were compared for their effectiveness in correcting the disturbances associated with diarrhoea induced by Escherichia coli. Each solution (saline, Hartmann's, Darrow's, Plasmalyte +/- glucose) was tested on eight Jersey calves less than a week old and weighing approximately 25 kg. Each calf received 8.5 litres over three days, at about 20 ml kg-1 h-1. Solutions such as saline or Plasmalyte which had higher concentrations of sodium were more effective at correcting dehydration and electrolyte disturbances than those with less sodium (Darrow's, Hartmann's) but only those with bicarbonate precursors (lactate, acetate, gluconate) were effective in correcting metabolic acidosis. The additional potassium in Darrow's was predictably unhelpful in correcting hyperkalaemia and the additional glucose in Plasmalyte-glucose, despite some beneficial effects, undermined its effectiveness in correcting acidosis. These results suggest that solutions for intravenous treatment should probably contain about 150 mmol litre-1 Na+, 5 mmol litre-1 K+ and about 50 mmol litre-1 of a mixture of bicarbonate and precursors. Neither of the commonly used solutions (saline or Hartmann's) is thus ideal.
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Sodium preference was examined in three groups of sheep which had all sustained two consecutive pregnancies and lactations on either adequate sodium intakes (group C) or low sodium diets (B and C). Group B received a potassium supplement as well as a low sodium diet during the present experiment. No convincing or sustained increase in sodium preference resulted from the reduction in body sodium caused by pregnancy and lactation in group B or C, whether the sodium solutions offered were 40 or 300 mmol/l. In a second experiment, sodium preference (sodium bicarbonate, 40 mmol/l) was studied throughout pregnancy in sheep on low or adequate sodium diets, also non-pregnant controls on low sodium diets. Again, pregnancy on a low sodium intake failed to intensify salt appetite except for a transient (but significant) peak around d90, close to the peak of aldosterone secretion; a similar increase in preference occurred on the adequate sodium diet. However, salt appetite failed to intensify during the period of peak sodium demand (the last third of pregnancy) whereas renal and faecal sodium conservation are appropriately increased.
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A low-sodium diet was given to Blackface ewes over two reproductive seasons. This diet provided a total of 3-7 mmol/d except during lactation when the intake was about 11 mmol/d. Control ewes were given the same diet supplemented with sodium chloride to provide recommended levels which were about tenfold that of the experimental diet. The output of Na in urine and faeces from ewes given the low-Na diet was very low, about 3 mmol/d, from early in the experiment and continued at about this level throughout. Lambs born to low-Na ewes and given a low-Na diet similar to that of their dams during lactation, grew, after weaning, more slowly than corresponding lambs from control ewes, but at 6 months of age when six from each group were killed, tissue Na contents were only slightly lower in experimental than control lambs. Fluids and tissues obtained at the end of the second lactation from four ewes of each group that had suckled twin lambs, were analysed for Na and potassium. The Na concentration in saliva and rumen fluid of low-Na ewes was about half that of control ewes and there were corresponding increases in K: the differences were significant. Although Na concentrations for experimental ewes were generally lower than those for control ewes in the tissues analysed (liver, kidney, heart, brain and bone), the difference was significant only for the heart (P less than 0.05). Haemoglobin and packed cell volume were significantly elevated in low-Na ewes (P less than 0.01), indicating decreased body fluid volume.(ABSTRACT TRUNCATED AT 250 WORDS)
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The hypothesis that the toxic effects of imidocarb mediated by reduced cholinesterase activity might be intensified by hypomagnesaemia was tested in calves. Hypomagnesaemia was induced in 12 males (50 kg) using an artificial milk based on a commercial nondairy coffee creamer. Although plasma magnesium levels reached 0.33 mmol litre-1 in two weeks no clinical signs were detected. In 12 control calves a daily magnesium supplement of 0.6 g was inadequate although the published requirement is 0.45 g; it was raised to 1.2 g to keep plasma magnesium normal. Lighter calves developed hypomagnesaemia more readily and fast-growing calves had lower plasma urea concentrations. Plasma calcium, but not plasma magnesium, showed significant positive correlation with plasma albumin. The only statistically significant effects of hypomagnesaemia were slight elevations of white cell count and plasma sodium. The hypomagnesaemic and normomagnesaemic calves were divided into two equal groups and treated with 3.3 mg kg-1 of imidocarb dipropionate or a placebo. The drug produced the expected clinical signs of mild toxicity and depression of cholinesterase but no other adverse effects. Transient slight depressions of plasma calcium and potassium concentration, a transient rise of plasma sodium and elevation of creatine kinase occurred. None of the effects of imidocarb treatment was intensified by hypomagnesaemia except, perhaps, constriction of the pupils; generally, hypomagnesaemic animals were affected less.
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