Cardio-pulmonary responses and gas exchange during exercise in adults with homozygous sickle-cell disease (sickle-cell anaemia)

Cardio-pulmonary responses and gas exchange during progressive exercise, the ventilatory response to hypercapnia and anthropometric indices were measured in twenty-two Jamiacan adults with homozygous sickle-cell disease. Their anthropometric indices and exercise performances were compared with those observed in healthy but sedentary adults in the Caribbean. The patients had long lower limbs for their height; their body fat, proportion of lean body mass as muscle and vital capacity reduced. Haemoglobin concentration ranged from 4 to 10g/100ml. Heart rate and ventilation were normal at rest. During exercise in the male patients haemoglobin concentrations below about 8g/100ml were associated with an increased demand for anaerobic metabolism. This resulted in excessive lac ticacidaemia and increased ventilation at standard oxygen uptake (hyperpnoea). The ventilation-tidal volume relationship was normal. When allowance was made for differences in body muscle, anaemia did not appear to affect the heart-rate response to exercise. Hyperventilation with respect to carbon dioxide output, increased alveolar-arterial oxygen-tension gradients and abnormal deadspace ventilation during exercise indicated a pulmonary perfusion disturbance with mixed venous shunting. The most likely basis for this disorder was considered to be the sickling phenomenon. Arterial hypoxaemia produced by the pulmonary shunt probably accounted for some of the exercise hyperpnoea, partly by increasing the chemoreceptor drive and partly by encouraging lacticacidaemia. Reduced arterial carbon dioxide tensions and bicarbonate concentrations had lowered the threshold and increased the sensitivity of the ventilatory response to carbon dioxide as measured by rebreathing. Increased chemosensitivity was not thought to have contributed towards the exercise hyperpnoea since arterial carbon dioxide tensions were below the threshold value for ventilatory drive. Exertional dyspnoea in sickle-cell disease was attributed to the combination of hyperpnoea and reduced maximum breathing capacity (MBC) owing to small lung volumes. The fraction of (MBC) used at standard work was therfore abnormally large, and the increased ventilatory effort produced a sensation of breathlessness in some patients (Summary)

Glucose tolerance and insulin sensitivity in malnourished children

In malnourished, compared with recovered children, fasting blood glucose concentrations were low and there was impared peripheral glycolysis as shown by a failure of blood lactate to raise after glucose was injected intravenously. Homogenates of muscle biopsies from malnourished and recovered children produced equal amounts of lactate when incubated anaerobically with various substrates, but when compared with homogenates of biopsies from normal children the pattern suggested an impairment of glycolysis. The rate of glucose disappearance after intravenous glucose was slow in the malnourished child and there was possibly diminished sensitivity to exogenous insulin. Isocaloric diets relatively high or low in fat were fed to children who had recovered from malnutrition. Glucose tolerance, insulin sensitivity, fasting plasma insulin and insulin response to intravenous glucose were all the same in children on either diet. (AU)

Carbohydrate metabolism in infantile malnutrition

It has been established that malnourished infants have various disorders of carbohydrate metabolism. The present studies were designed to investigate the cause of impaired glucose tolerance which has previously been described. Glucose was given intravenously to children when malnourished and after recovery. Blood glucose, pyruvated and lactate were measured. There was no difference between the two groups in initial lactate or pyruvate levels, and there was no significant rise in either after glucose in malnourished infants; in contrast the recovered children showed significant increases in both pyruvate and lactate. Next in vitro lactate production from various substrates was measured from muscle homogenates. With all substrates used there was difference in lactate production between malnourished and recovered children. However, muscle samples from healthy children showed significantly higher lactate production from all substracts. Insulin sensitivity was assessed by measuring the disappearance of inject glucose after intravenous insulin. Glucose disappearance after insulin was prolonged in the malnourished children. The data suggests that the glucose intolerance of malnutrition is the result of insulin insensitivity (AU)

Alterations in carbohydrate metabolism in Jamaican children with severe malnutrition

Carbohydrate metabolism was studied in Jamaican children who had been admitted to hospital with protein-calorie malnutrition. Analysis of liver biopsies showed that levels of protein and glycogen were low in malnutrition and rose with recovery. Hepatic glucose-6-phosphatase was elevated in malnutrition but phosphorylase levels were normal. In the malnourished child there was normal hepatic glycogenolysis as shown by a normal blood glucose response to intravenous glucagon without any detectable rise in blood pyruvate and lactate. Fasting levels of blood lactate as well as lactate-pyruvate ratios rose with recovery from malnutrition. Galactose tolerance tests showed a delayed disappearance of injected galactose, but the maximum increase in blood glucose after galactose injection was the same in all clinical states. Glucose disappearance was delayed after both glucagon and galactose. Muscle glycogen was initially reduced, but there was a markeed "overshot" to supranormal levels during the recovery phase. (AU)