Plasma concentration was measured after rectal and nasogastric administration of paracetamol 15 mg/kg to 28 febrile children aged between 9 days to 7 years who had undergone cardiac surgery. After equivalent doses, rectal administration in neonates and children on the first postoperative day was found to produce plasma concentrations below the therapeutic range with higher concentrations after nasogastric paracetamol on the second postoperative day. There was less variance in plasma paracetamol concentrations in neonates. Both plasma elimination half life and area under the plasma concentration time curve were significantly increased in neonates after suppository dosing compared with older children. There was no difference in antipyretic effect between the two routes of administration, but this was much lower than that previously reported in febrile children.
1. Dobutamine in 5% (w/v) D-glucose was infused at sequential doses of 2, 5 and 10 micrograms min-1 kg-1, 45 min at each dose, into eight healthy male subjects, and the effects were compared with those produced by infusion of the corresponding volumes of 5% (w/v) D-glucose alone. 2. The energy expenditure increased and was 33% higher than control (P less than 0.001) at 10 micrograms of dobutamine min-1 kg-1. The respiratory exchange ratio decreased from 0.85 (SEM 0.02) before infusion to 0.80 (SEM 0.01) at 10 micrograms of dobutamine min-1 kg-1, but did not alter during the placebo infusion (P less than 0.001). 3. Plasma noradrenaline concentrations were lower during the dobutamine infusion compared with during the infusion of D-glucose alone (P less than 0.025). Plasma dopamine concentrations remained below 0.1 nmol/l throughout both infusions. 4. Compared with during the placebo infusion, the blood glucose concentration decreased (P less than 0.001), the plasma glycerol and free fatty acid concentrations increased by 150 and 225%, respectively (both P less than 0.001), and the plasma potassium concentration decreased from 3.8 (SEM 0.07) to 3.6 (SEM 0.04) mmol/l (P less than 0.01) during dobutamine infusion. The plasma insulin concentration increased at 2 and 5 micrograms of dobutamine min-1 kg-1 (P less than 0.001) with no further rise at 10 micrograms of dobutamine min-1 kg-1. 5. Compared with during the placebo infusion, the systolic and diastolic blood pressures and the heart rate increased during dobutamine infusion (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Segments of the small intestine have been kept exsected at different temperatures to determine for how long a period the pendulum movements can be revived when the intestine is subsequently put into oxygenated Locke's solution at 37° C.; also to determine what modifications the pendulum movements undergo when revived under these conditions, and what alterations occur in the effects produced on them by certain drugs. As far as has been found, the maximum time of survival is as follows: 5 days when the isolated intestine is kept at 3° to 7° C.; over 24 hours when kept at about 15° C.; at least 8½ hours when kept at 37° C. (without oxygen). The movements of the revived intestine show a gradual diminution of amplitude, but no conspicuous alteration of rate. The reaction of the revived intestine to adrenine and to barium continues unchanged at those temperatures so long as the intestine retains any power of rhythmic movement. Pilocarpine and atropine produce their normal action on the pendulum movements when the intestine is kept for 5 days at 3° to 7° C.; but lose their effect when it is kept for 3½ hours at 37° C. The results give an indication of the longevity of the receptive substances for those drugs when the intestine is kept at different temperatures, and lead to the conclusion that the receptive substances connected with the sympathetic nerve terminals have a greater vitality than those connected with the parasympathetic nerve terminals. The isolated circular muscle of the cat's small intestine possesses the power of executing rhythmic movements, resembling the pendulum movements, when it is completely separated from the longitudinal muscle on the one side and from the submucosa and mucous membrane on the other. This power is retained even when the outer layers of the circular muscle have also been removed; the inner layers, remote from Auerbach's plexus, still retain the property of spontaneous rhythmicity. Subject to a revision of the accepted conceptions of the localised nature of Auerbach's plexus, the conclusion is drawn that the spontaneous rhythmicity of these movements is an inherent property of the muscle itself. This conclusion is supported by the fact that, when the intestine is kept at different temperatures, the power of executing rhythmic movements and the power of reacting to barium disappear at the same time. The movements of the isolated muscularis mucosæ of the cat's small intestine have been recorded and found to consist of regular slow rhythmic contractions, occurring at the rate of one in 27 to 60 seconds. Those movements bear a general resemblance to the rhythmic contractions of the spleen, and probably have a similar function of accelerating the local circulation. Adrenine has a motor effect on the rhythmic contractions of the muscularis mucosæ, as on those of the spleen. The benefit of adrenine as a styptic in gastric ulcer may be due partly to its arresting capillary hæmorrhage by contracting the muscularis mucosæ.
1. Patients suffering trauma and sepsis are insulin resistant, but no studies have specifically been made of patients suffering multiple organ failure. 2. We have studied exogenous glucose utilization in multiple organ failure using a combination of the hyperglycaemic glucose clamp and indirect calorimetry to quantify glucose utilization in multiple organ failure, partitioning it into oxidative and nonoxidative disposal (storage). 3. Fourteen septic patients with multiple organ failure were studied. APACHE II (Acute Physiological and Chronic Health Evaluation Mark II) scores on the day of the study ranged from 11 to 31 (median 16). Twenty percent D-glucose was infused and blood glucose was clamped at 12 mmol/l for 3 h. The results were compared with those obtained on seven healthy control subjects. 4. Glucose utilization and energy expenditure were similar in the two groups for the first 90 min of the clamp, after which glucose utilization and energy expenditure increased steadily in the control subjects but did not change in the patients. Respiratory exchange ratio rose in both groups; considered over the whole of the clamp period, respiratory exchange ratio was slightly lower in the patients than in the control subjects (P < 0.05) but not at any specific time point. Glucose oxidation rose in both groups but non-oxidative glucose disposal (storage) rose only in the control subjects. Glucose oxidation was slightly lower in the patients (P < 0.05) but not at any specific time point and there was no difference between the groups in the amount by which glucose oxidation increased. Non-oxidative disposal in the patients fell significantly (P < 0.01) over the course of the clamp and was significantly lower than in the control subjects (P < 0.01). 5. Growth hormone increased in response to glucose infusion in the patients but not in the control subjects. 6. Like patients suffering uncomplicated sepsis or trauma, patients with multiple organ failure are also insulin resistant. The defect appears to lie in an impairment of the ability to store glucose rather than oxidize it, and this may be due in part to the increase in growth hormone in patients with multiple organ failure.
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