1. Our objectives were to measure total energy expenditure, the daily variation in total energy expenditure and the physical activity level in a group of HIV-positive subjects using the bicarbonate-urea method. The study also aimed to assess the practicalities of using the bicarbonate-urea technique in free-living conditions. 2. Total energy expenditure was measured with the bicarbonate-urea method over 2 consecutive days (1 day in one subject) in 10 male patients with HIV infection (median CD4 count = 30). Resting energy expenditure was measured by indirect calorimetry. Physical activity level (total energy expenditure/resting energy expenditure) was calculated from these measurements and from activity diaries. 3. Resting energy expenditure was found to be 7.46 ± 0.87 MJ/day, 5% higher than predicted values. Total energy expenditure was 10.69 ± 1.95 MJ/day with an intra-individual day-to-day variation of 6 ± 6%. The measured physical activity level was 1.42 ± 0.14, higher than the diary estimate of 1.34 ± 0.16 ( P = 0.029), and there were large inter-method differences in individual values. The subcutaneous infusion of bicarbonate was well tolerated and did not seem to restrict normal activities. 4. Total energy expenditure was not elevated in the group of HIV-positive subjects when compared with reference values for normal subjects. The physical activity level of the patients in this study was lower than that measured using other techniques in healthy young men, but was compatible with that expected for people leading a sedentary lifestyle. Reductions in physical activity in patients with HIV are likely to contribute to the wasting process and physical activity level may thus be a clinically useful measure. This study has also provided the first tracer estimate of the day-to-day variation in total energy expenditure. The bicarbonate-urea method represents an important new investigative tool for measuring total energy expenditure which has previously only been possible within the confines of a whole-body calorimeter or using the expensive doubly labelled water method.

1. Rats established on a normal (20% protein) diet or a protein-deficient (3% protein) diet were given either a subcutaneous injection of turpentine (5 ml/kg), which induces formation of aseptic abscesses, or saline. Plasma samples were obtained at timed intervals (0–14 days) after the injection for determination of albumin, total protein, α 2 -macroglobulin (a major acute-phase protein in the rat) and interleukin-6 concentrations. The magnitude and pattern of the acute-phase protein response was then compared with the local inflammatory reaction, assessed histologically, and with changes in the circulating concentration of interleukin-6, which is an important mediator of the acute-phase protein response. 2. After turpentine injection there was an early fall in the plasma albumin and total protein concentrations in both normal and protein-deficient rats. After 12 h the total protein concentration increased in both groups of animals reaching a peak at about 48 h, whereas the plasma albumin concentration continued to fall reaching a minimum at 48 h. The main α 2 -macroglobulin response was delayed and attenuated in the protein-deficient rats (onset 9 versus 24 h, peak concentration 8.95 ± 0.5 versus 5.33 ± 0.75 g/l, P <0.01, and area under the concentration-time curve 18.43 ± 2.13 versus 7.96 ± 1.48 gl −1 days, P <0.01, in the normal group and protein-deficient group, respectively). 3. The circulating interleukin-6 concentration showed a transient early rise at 1 h, and was followed by a larger more sustained peak at 6–48 h. The onset of the secondary rise preceded the onset of the α 2 -macroglobulin response in both groups of animals, but both the onset and rate of rise were slower in the protein-deficient animals. The peak concentration of interleukin-6 and the area under the concentration-time curve were not significantly different between the groups. There were also no obvious differences in the intensity of the local inflammatory reaction, although the onset of repair was delayed in the protein-deficient animals. 4. This study confirms that the acute-phase protein response is attenuated by protein deficiency, but this does not appear to be due to an attenuated local inflammatory response after turpentine injection. The delayed onset of the interleukin-6 response may explain the delayed onset of the acute-phase response, but the overall magnitude of the interleukin-6 response (total area under the concentration-time curve), which was similar in the two groups, does not explain the overall attenuation of the α 2 -macroglobulin response.

1. A solid-phase radioimmunoassay is described for the estimation of the uncoupling protein content of human brown adipose tissue mitochondria, as an index of thermogenic capacity. 2. The concentration of inner mitochondrial membrane uncoupling protein was measured in brown adipose tissue samples from 48 individuals who died suddenly. 3. The uncoupling protein content of axillary adipose tissue was greater than that of perirenal adipose tissue. 4. Variations in brown adipose tissue uncoupling protein content, which would be consistent with changing thermogenic requirements and capacity, were observed in different groups of subjects. Significantly lower concentrations were found in adults and in pre-term and stillborn infants than in older infants and children.

1. The responses to stimulation of both cardiac and lymphocyte β-adrenoceptors were studied in 23 normal subjects and 23 with untreated essential hypertension. Lymphocyte cyclic adenosine monophosphate was measured in vitro after incubation with isoprenaline (0.01 μmol/l-10 mmol/l). There were no significant differences between the amount of cyclic adenosine monophosphate generated by lymphocytes in the two groups in the isoprenaline concentration range 0.01 μmol/l-1 mmol/l. 2. In the same subjects we compared cardiac β-adrenoceptor-mediated responses using the change in heart rate after bolus doses of isoprenaline (dose range 0.25–3 μg). In 12 subjects (six normotensive, six hypertensive) we studied the heart rate responses to isoprenaline before and after ‘total’ autonomic block (0.04 mg of atropine/kg and 300 μg of clonidine). The latter permitted assessment of intrinsic cardiac responsiveness after eliminating cardiovascular reflexes. 3. In subjects with reflexes intact the rise in heart rate was significantly greater in normal than in hypertensive subjects at all doses of isoprenaline. Isoprenaline evoked a similar dose-related fall in blood pressure in both groups, which contributed to the reflex drive. After autonomic block the differences in heart rate responses were no longer present. 4. The results indicate that the reduced tachycardia at a given dose of isoprenaline in hypertensive subjects is due to impairment in their baroreceptor—heart rate reflex since this was no longer present after atropine and clonidine. 5. The absence of any intrinsic difference in cardiac β-adrenoceptor responsiveness is in agreement with the results with lymphocytes.

1. The rates of entry of noradrenaline to plasma and of removal of noradrenaline from plasma, and plasma noradrenaline concentration, were determined in normal subjects and in patients with essential hypertension. Neuronal uptake of noradrenaline was assessed from the plasma tritiated noradrenaline disappearance curve, after infusion to steady state. 2. Noradrenaline disappearance was biexponential. Rapid removal was dependent on neuronal uptake, being slowed if neuronal noradrenaline uptake was reduced, either by desipramine in normal subjects, or in patients with sympathetic nerve dysfunction (autonomic insufficiency). 3. In 10 of 41 hypertensive patients the t 1 1/2 similarly was prolonged, presumptive evidence of a defect in neuronal noradrenaline uptake. Endogenous noradrenaline escaping uptake after release, and spilling over into plasma, and plasma noradrenaline concentration, were increased in these patients. 4. Defective neuronal uptake of noradrenaline, by exposing adrenoreceptors to high local transmitter concentration, may be important in the pathogenesis of essential hypertension in some patients.