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Biomedical subjects

I T Campbell

Publications and source records attributed to I T Campbell.

At least 19 recordsLinked to original sources

The performance of a variable-flow indirect calorimeter.

Indirect calorimetry estimates energy expenditure from measurement of respiratory gas exchange volumes. This paper considers the design and evaluation of an indirect calorimeter, the Europa GEM, suitable for use in nutritional research. The calorimeter is of the ventilated hood, flow-through type and is intended for use with spontaneously breathing patients. Our aim was to develop an accurate, flexible instrument with a high level of automation. Performance was assessed in a laboratory simulation using reference gas injections (n = 24) producing a mean error of 0.3 +/- 2% in oxygen consumption (VO2), 1.8 +/- 1% in carbon dioxide production (VCO2) and 1.4 +/- 1.5% in respiratory quotient (RQ). In order to investigate the effect of FeCO2 on error multiplication a further subdivision (n = 8) of tests at FeCO2 = 0.5%, 0.75% and 1% was made by modulating the air flow through the hood. However, the predicted increase in system accuracy with increasing FeCO2 was not apparent in practice.

Calorimetry, Indirect

Septic patients in multiple organ failure can oxidize infused glucose, but non-oxidative disposal (storage) is impaired.

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.

Adolescent

Muscle thickness, measured with ultrasound, may be an indicator of lean tissue wasting in multiple organ failure in the presence of edema.

Multiple organ failure (MOF) is accompanied by muscle wasting, but changes in body composition are frequently obscured by fluid retention (edema), mainly in superficial and visceral tissue. There is a need to assess body composition and changes in body composition in these circumstances independently of edema. A relation was sought between fat-free (lean tissue) mass [calculated from body weight and skinfold thicknesses and measured by using dual-energy X-ray absorptiometry (DXA)] and muscle thickness (measured using ultrasound at a variety of sites accessible in an unconscious supine subject) to determine which sites correlated best with lean body mass. The three best sites were midbiceps, midforearm anteriorly, and midthigh anteriorly: R2 for the simple sum of the three sites correlated with fat-free mass from skinfold thicknesses was 71.1%, and with lean tissue mass from DXA was 76.1%. Serial measurements of both muscle thickness and midupper-arm circumference in nine patients with MOF showed a complete dissociation; in all nine there was a significant negative correlation of muscle thickness with time (P < 0.05) but changes in arm circumference were random. Only one patient showed a significant negative correlation with time, seven showed no change, and one other showed a significant increase. The muscle thicknesses that correlate best with lean body mass are measured over the biceps, anterior forearm, and anterior thigh. Monitoring muscle thicknesses at these three sites identifies wasting in edematous patients as it is happening.

Absorptiometry, Photon

Manipulation of substrate utilization with somatostatin in patients with secondary multiple organ dysfunction syndrome.

OBJECTIVES: To determine whether glucose utilization and metabolic substrate (glucose and fat) oxidation could be manipulated in patients with secondary multiple organ dysfunction syndrome. DESIGN: Prospective study. SETTING: Intensive care units (ICU) of two university hospitals. PATIENTS: Eight adults free of hepatic disease and hemodynamically stable at the time of study, but with failed respiratory and gastrointestinal systems, who thus required mechanical ventilation and intravenous nutrition. INTERVENTIONS: Patients were infused with 20% dextrose through central venous cannulas at rates that increased and maintained (clamped) their plasma glucose concentration at 216 mg/dL (12 mmol/L) for 3 hrs. Somatostatin was infused continuously during the second and third hours of the clamp to reduce plasma concentrations of endogenous insulin and glucagon. Exogenous insulin was administered together with somatostatin during the third hour to restore basal insulin concentrations. Energy expenditure was measured by indirect calorimetry throughout the study and blood samples were withdrawn regularly for determination of metabolite and hormone concentrations. Main statistical comparisons were made between the baseline data (first hour of the study) and data collected during the second and third hours of the clamp. MEASUREMENTS AND MAIN RESULTS: Plasma glucagon concentrations were reduced by nearly 50% (p < .05) toward the end of the study, whereas no significant changes in plasma concentrations of cortisol or growth hormone occurred. Energy expenditure did not change significantly at any time during the clamp procedure. Glucose utilization (6.1 mg/kg/min [34 mumol/kg/min]) during the first hour of the hyperglycemic clamp, decreased by 53% (p < .05) with the infusion of somatostatin during the second hour of the clamp. However, once exogenous insulin was infused during the third hour, glucose utilization increased by 55% (p < .05) when compared with the baseline (hour 1) rate. Glucose oxidation was nearly doubled during the third hour of the study when compared with oxidation rates during the first and second hours. Fat oxidation decreased steadily during the 3-hr clamp. CONCLUSIONS: Glucagon has a significant inhibitory effect on glucose utilization during intravenous glucose infusion in the multiple organ dysfunction syndrome patient. Pharmacologic intervention with somatostatin and insulin (physiologic dose) can facilitate glucose utilization and oxidation in these patients. Further investigations are needed to determine whether long-term alteration of glucose and fat metabolism would be beneficial in the patient with secondary multiple organ dysfunction syndrome.

Aged

Hormonal and metabolite responses to glucose and maltodextrin ingestion with or without the addition of guar gum.

The purpose of this study was to examine the effects of ingesting water (P), a glucose solution (GL), a maltodextrin solution (Md), a glucose solution with 8% guar gum (GL+G), and a maltodextrin solution with 8% guar gum (Md+G), on the hormonal and metabolite responses during cycling, and on subsequent time to exhaustion. Five male subjects undertook five 90 min rides on a bicycle ergometer at an exercise intensity corresponding to 65% VO2max after having ingested 1 g.kg-1 body weight of the test product in 400 ml of water immediately before the exercise. Blood samples were taken during the trials for analyses of adrenaline, noradrenaline, insulin, glucagon, glucose, lactate and non-esterified fatty acids (NEFA). Respiratory measures were also undertaken during the trials for the determination of oxygen consumption (VO2) and respiratory exchange ratio (RER), from which the carbohydrate oxidation rates were calculated. Rates of perceived exertion (RPE) were also assessed. Ten minutes after the 90 min ride, subjects exercised to volitional exhaustion at an exercise intensity of 75% VO2max. ANOVA revealed that there were significant differences between the treatments for adrenaline (p < 0.01), insulin (p < 0.05), glucose (p < 0.01), lactate (p < 0.01), NEFA (p < 0.01), RER (p < 0.001) and carbohydrate oxidation rate (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Efficiency of the Carden "Ventmasta" in A and D modes during controlled ventilation in children.

We have determined the efficiencies of the enclosed Mapleson A and Mapleson D modes of the Carden "Ventmasta" ventilator during controlled ventilation in 19 anaesthetized children. In addition, we determined the suitability for the A mode of the fresh gas formula, VF = 0.6 x weight0.5. Efficiency was assessed in terms of the fraction of fresh gas delivered to the alveoli. When the minute volume to fresh gas flow ratio exceeded 1.5, fractional delivery of fresh gas was 23% greater in the A mode than in the D mode (0.74 vs 0.60) (P < 0.0001). Under the same conditions, mean end-tidal carbon dioxide concentration in 27 children undergoing ventilation in the A mode with VF = 0.6 x weight0.5 was 4.6% (range 3.5-5.4%). We conclude that the Carden system is up to 23% more efficient in the A mode than in the D mode, and that under the conditions of this study, normocapnia or mild hypocapnia was produced accurately using the formula VF = 0.6 x weight0.5.

Adolescent

Respiratory function after injection sclerotherapy of oesophageal varices.

Arterial oxygen tension (Pao2), carbon dioxide tension (PaCO2), and vital capacity were measured preoperatively and one day postoperatively in patients with chronic hepatic cirrhosis having elective oesophageal injection sclerotherapy under general anaesthesia. The results were compared with the same measurements made in patients with chronic cirrhosis anaesthetised and scheduled to have injection sclerotherapy under general anaesthesia but who, because of variceal obliteration, only had an oesophagogastroscopy. In the injected group PaO2 decreased by 9.3 (3.0) mm Hg (1.2 (0.4) kPa) (mean (SEM)) (p < 0.02) but in the controls did not change. The difference between the two groups was significant (p < 0.02). Vital capacity decreased by 0.39 (0.08) litres (BTPS) (p < 0.01) after injection sclerotherapy but in the controls did not change. Again the difference between the two groups was significant (p < 0.02). In the injected group there was a significant correlation between the change in PaO2 and the percentage change in vital capacity (r = 0.787, p < 0.01) but no such relation was seen in control subjects. These results suggest that oesophageal injection sclerotherapy is associated with a restrictive defect in respiratory function one day after the injection caused, possibly, by sclerosant embolising to the lung.

Esophageal and Gastric Varices

Determination of the onset of rebreathing in an enclosed afferent reservoir breathing system in anaesthetized, spontaneously breathing adults: a comparison of three methods.

We used three methods to determine the onset of rebreathing in the Ohmeda enclosed afferent reservoir breathing system and compared the results with the previously published rebreathing characteristics of this system. Of the methods studied, expiratory limb capnography proved unsuitable for determining the onset of rebreathing in this system. Inspiratory limb capnography and minimum inspired carbon dioxide at the mouth did enable the onset of rebreathing to be determined. However the fresh gas flow:minute volume ratio at which rebreathing occurred as determined by these criteria was less than that determined by the Kain and Nunn criteria and thus offer no clinical advantage over the latter.

Adult

Increased whole body protein breakdown predominates over increased whole body protein synthesis in multiple organ failure.

1. Whole body protein turnover was measured using a primed-constant infusion of L-[1-13C]leucine with measurement of breath 13CO2 production and plasma 13C alpha-ketoisocaproate enrichment. Ten fasting patients, requiring mechanical ventilation and suffering from multiple organ failure, and six healthy control subjects were studied. 2. Protein breakdown and leucine removal from the plasma for protein synthesis were significantly higher in the patients than in the control subjects (P < 0.01). In addition, leucine oxidation was almost 75% higher in the patients than in the healthy control subjects (P < 0.05). 3. Plasma concentrations of glucose, insulin and growth hormone were not different between the two groups, but those of glucagon (not significant), noradrenaline (P < 0.05) and cortisol (P < 0.01) were almost two- and three-fold higher in the patients than in the control subjects. 4. Mean energy expenditure, measured by indirect calorimetry, was 30% higher in the patients than in the healthy control subjects (P < 0.01). 5. Combining the data from both groups of subjects and using multiple regression analysis, cortisol was found to be the most significant predictor of (i) protein breakdown (48% of variance explained), (ii) leucine oxidation (69%) and (iii) hourly energy expenditure (54%). 6. The present investigation using [13C]leucine tracer methods demonstrated, in patients with multiple organ failure, that whole body protein breakdown and synthesis increased concomitantly and were twice as high as rates measured in healthy control subjects. Of the hormones measured in the present study, cortisol appears to have the most significant effect on whole body protein turnover.

Adult

Fresh gas requirements of an enclosed afferent reservoir breathing system in anaesthetized, spontaneously breathing adults.

Using two methods of determining the onset of rebreathing, we have determined the minimum fresh gas flow rate (VF) of the Ohmeda enclosed afferent reservoir breathing system (EAR) in anaesthetized, spontaneously breathing adults. Rebreathing as defined by the Kain and Nunn criteria did not occur when the VF/VE ratio was greater than 0.70. A mathematical model was used to calculate the degree of rebreathing at each VF. From this model, rebreathing did not occur when VF was 0.86 VE or more and this value of VF/VE is considered appropriate to eliminate rebreathing in clinical practice.

Aged

Metabolic effects of dobutamine in normal man.

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)

Adult

Pregnant women with endemic pemphigus foliaceus (Fogo Selvagem) give birth to disease-free babies.

Endemic pemphigus foliaceus (PF), also known as Fogo Selvagem (FS), is an organ-specific autoimmune disease mediated by autoantibodies. These autoantibodies are disease specific, predominantly restricted to the IgG4 subclass, and pathogenic, as demonstrated by passive transfer studies. In contrast to pemphigus vulgaris, neonatal skin disease does not appear to occur in babies born to mothers with non-endemic PF or FS. In the present study we have examined 19 mother/neonate pairs where the mother had documented FS. Mothers and neonates were examined soon after delivery and tested by immunofluorescent (IF) techniques for FS autoantibodies either in circulation (mothers' sera or babies' cord blood) or bound to the neonatal epidermis. All neonates included in this study were born with normal skin. Twelve biopsies from 17 neonates showed negative direct IF using both FITC-antihuman IgG or monoclonal anti-IgG subclass antibodies. In five biopsies the epidermal ICS of the babies showed weak staining. In 10 of the 19 cord sera tested, FS IgG autoantibodies were undetectable; in nine, these autoantibodies were present in low titers (less than 1:40). The sera of the mothers showed higher titers of FS autoantibodies, and IgG4 was the predominant IgG subclass autoantibodies. It appears that human placenta may modulate the expression of disease in the newborn by operating as a "biologic immunoadsorbent" of pathogenic autoantibodies.

Adult