Resting energy expenditure in females with cystic fibrosis: is it affected by puberty?

OBJECTIVE: The aims of this study were to determine the effect of puberty and the menstrual cycle on resting energy expenditure (REE) in females with cystic fibrosis (CF). DESIGN: Cross-sectional study. All participants had measurements of REE, anthropometry and pubertal staging. The measurements in the postmenarche group were carried out both in the follicular and luteal phases of their menstrual cycle. SETTING: CF outpatient clinic at the Children's Hospital at Westmead. SUBJECTS: Fifty-six females with CF and pancreatic insufficiency (13 postmenarche) were recruited from the hospital clinic and 63 controls (21 postmenarche) were recruited through families and friends of hospital staff. RESULTS: Females with CF had a higher REE than controls (111.6+/-12.8% of predicted from controls P<0.001). There was a significant effect of menarche on REE with a decrease in the postmenarche -470 kJ/24 h compared with premenarche after adjustment for fat-free mass, fat mass and group (control or CF). There was no difference in REE between the follicular and luteal phases for either CF or controls. CONCLUSIONS: Females with CF had raised REE that appeared to be independent of menarche. This study implies all females with CF and pancreatic insufficiency may need more intensive dietary management, owing to raised REE, to maintain growth and nutritional status, and possibly improve survival.

Parallel secretion of pancreatic phospholipase A(2), phospholipase A(1), lipase, and colipase in children with exocrine pancreatic dysfunction.

The cosecretion of pancreatic lipase and colipase are important in normal fat digestion. As adsorption of phosphatidylcholine to the lipid substrate interferes with lipase activity, hydrolysis to lysophosphatidylcholine with subsequent desorption is also essential for fat digestion. There are some data regarding the secretion of pancreatic phospholipases in normal adults but none in children or patients with pancreatic disease. In the present study, we aimed a) to develop an accurate fast assay method to measure phospholipase A(2) and b) to determine the secretion rate of pancreatic phospholipase A(2) and whether it is cosecreted with lipase and colipase in children with exocrine pancreatic dysfunction. Nine male patients aged 0.5 to 16 y (seven with cystic fibrosis, two with malabsorption) underwent pancreatic stimulation tests. Their colipase and lipase secretion rates were measured by titrimetric methods and phospholipase A(2) and A(1) by phosphorus magnetic resonance spectroscopy ((31)P NMR). It was found that the phospholipases, colipase, and lipase were absent in the two patients with pancreatic insufficiency. In patients with normal absorption, there were marked inter-and intrasubject variations of lipase, colipase, and phospholipase secretion rates that were consistent with the degree of exocrine pancreatic dysfunction. However, in the three 20-min stimulation periods of the pancreatic function test, pancreatic phospholipase is cosecreted with lipase and colipase, and average colipase and phospholipase A(2) secretion rates follow a similar or parallel pattern. These findings are consistent with the important role of pancreatic phospholipases in intestinal phospholipid hydrolysis leading to the desorption of phospholipids from the lipid substrate and enhancing lipid hydrolysis and phospholipid absorption.

Phospholipid changes in children with pancreatic sufficiency and insufficiency.

The phospholipid secretion rates and phospholipase A1 and phospholipase A2 activities in biliary-pancreatic secretions of patients with pancreatic sufficiency and insufficiency were measured using 31P-NMR spectroscopy. It was possible to quantify conveniently the individual phospholipids without prior extraction of lipids or treatment of the samples with detergent. The reciprocal nature of the decrease in phosphatidylcholine concentration, compared with the increase in the concentration of 1-lysophosphatidylcholine and 2-lysophosphatidylcholine, suggested a substrate/product relationship consistent with the activities of phospholipase A1 and phospholipase A2, respectively. Although the secretion rates of total biliary phospholipids among the patients with pancreatic sufficiency were similar, the phospholipase A1 and phospholipase A2 activities varied considerably. The latter differences were similar to their pancreatic lipase and colipase secretion levels and hence their degree of pancreatic dysfunction. The biliary-pancreatic secretions from patients with pancreatic insufficiency showed no enzyme activities. Total biliary phospholipid secretions in patients with pancreatic insufficiency with common bile duct stenosis were significantly lower than those in patients with pancreatic sufficiency, and pancreatic insufficiency without common bile duct stenosis.

Hepatobiliary disease in cystic fibrosis patients with pancreatic sufficiency.

Focal and multilobular biliary cirrhosis are considered pathognomonic of cystic fibrosis (CF) and almost invariably have been reported in patients with steatorrhea. In contrast, patients with pancreatic sufficiency and normal absorption are considered less likely to develop liver or biliary tract problems. The authors report three patients with CF and pancreatic sufficiency, presenting with recurrent abdominal pain (unrelated to pancreatitis). All had common bile duct disease, one with multilobular cirrhosis and portal hypertension. Pancreatic sufficiency was proven by quantitative pancreatic stimulation tests, 3-day fecal fat analyses, and serum pancreatic isoamylases. All three patients had mild lung disease. Two were homozygous for the common delta F508 mutation, and the other, a delta F508 compound heterozygote. Hepatobiliary structure and function were determined by serial hepatobiliary scintigraphy, percutaneous transhepatic cholecystography, and biochemical liver function tests. Patients 1 and 3 had mild hepatomegaly, normal liver biochemistry, and distal common bile duct strictures. Patient 2 had a firm nodular liver with splenomegaly, abnormal liver biochemistry, and a cholangiographic appearance of sclerosing cholangitis. All have undergone operative treatment for persistent abdominal pain. These cases confirm the occurrence of common bile duct pathology and liver disease in patients with CF and pancreatic sufficiency. They demonstrate that liver and biliary tract disease can occur independently of the underlying disease severity and the presence of steatorrhea. Further, they suggest that obstruction of the biliary tract may be an additional factor in the evolution of liver disease in CF.

Pancreatic function in infants identified as having cystic fibrosis in a neonatal screening program.

The use of the dried-blood immunoreactive-trypsin assay for the detection of cystic fibrosis in newborns has been questioned on the grounds that it may fail to identify patients with enough pancreatic function to have normal fat absorption. To investigate this possibility, we assessed pancreatic function in 78 patients identified in a neonatal screening program as having cystic fibrosis. The diagnosis of cystic fibrosis was confirmed by abnormal results on a sweat chloride test. The results of measurements of fecal fat excretion, pancreatic-stimulation tests, and estimations of the serum level of pancreatic isoamylase indicated that 29 of the 78 children (37 percent) had substantial preservation of pancreatic function. These children (median age, four years) had growth that was close to normal and comparable to growth in children with severe pancreatic insufficiency who received oral enzyme therapy. Pancreatic insufficiency subsequently developed in 6 of the 29 patients, at 3 to 36 months of age. We conclude that the serum immunoreactive-trypsin assay used in neonatal screening programs identifies patients with cystic fibrosis who have sufficient pancreatic function to have normal fat absorption and that a substantial proportion of infants identified as having cystic fibrosis are in this category.

Nutritional status, growth and development in children undergoing intensive treatment for cystic fibrosis.

Dietary intakes were measured over a period of 5 days in 36 malnourished and 36 well-nourished patients with cystic fibrosis. Both energy and protein intakes were significantly less in the malnourished patients for the two age groups studied: 4-9.99 years (p less than 0.01 for both parameters), and 10-16 years (p less than 0.05 and p less than 0.01, respectively). In both age groups and both patient groups, average protein intakes were well in excess of the recommended daily intake, but energy intake in the malnourished patients was below the recommended daily intake. Nutritional supplementation of 10 malnourished patients with a polymeric formula, infused overnight via a gastrostomy tube, resulted in a seven-fold increase in weight gain (p less than 0.001) and a doubling of linear growth velocity (p less than 0.01) over a period of 18 months, compared to the 18 months prior to gastrostomy feeding. Measurements of total body nitrogen in eight of these patients demonstrated a 38% increase in body nitrogen content over 12 months, indicating a replenishment of the protein deficit.

Chronic undernutrition/growth retardation in cystic fibrosis.

There is now sufficient evidence to prove that the maintenance of a high energy normally balanced diet prevents malnutrition/growth retardation and may well enhance prognosis in patients with CF. Most patients are able to tolerate the normal to high fat content without undue problems with steatorrhoea and with the recent advent of more effective enzyme replacement therapy, this should be even less of a problem. Conversely, there is an equally large bulk of evidence to indicate that the maintenance of a low fat diet, while controlling symptoms from steatorrhoea in some patients, is energy depriving and produces growth failure. In children or teenagers who are presently growth retarded, installation of a high energy intake may improve growth in some, but not in others. Further investigation of the latter patients is required to evaluate their persistent anorexia and advantages and disadvantages of nutritional supplementation by invasive techniques. Certainly growth and wellbeing can be vastly improved. However, such studies may well have to be multicentered to obtain sufficient patients to control for the many variables involved, in order to demonstrate the effects on pulmonary function.

Levels of glycolytic enzymes in the red blood cells of Australian Aborigines.

Blood samples wer collected from three populations of full-blood Aborigines, and twelve different enzymes were assayed in red blood cells. These results were compared with those of Caucasian controls. In the majority of enzymes studied significant differences were observed between the Aboriginal populations and also between individual Aboriginal populations and the Caucasian controls.

A kindred with red cell pyruvate kinase deficiency.

A case is described of mild haemolytic anaemia in a female homozygous for pyruvate kinase deficiency, with 20% of normal enzyme activity and with the unexplained associations that she suffers from angina pectoris and that three of her children died in childhood from a muscular dystrophy presumed to be Werdnig-Hoffman disease.

Red blood cell glycolysis and potassium type in sheep.

Based on the observations made on human and dog red blood cells, it was recently proposed that the response of red cell glycolysis to variations in the levels of specific cations in an evolutionary adaptation in response to a specific cellular environment. We have now examined the effect of K+ and Na+ on the activity of pyruvate kinase (PK) in the red blood cells from 2 genetically different types of sheep high potassium (HK) and low potassium (LK). The results indicate that K+ stimulate glucose consumption and the activity of PK in both types of sheep. It thus appears that red cell PK from LK sheep does not fit into the concept of cellular environment and PK activity.

Erythrocyte 2,3-diphosphoglycerate in anaemic sheep.

Experimental anaemia resulted in an increase of red cell 2,3-DPG from 0.11 micronM/g Hb to 0.99 micronM in haemoglobin A sheep and from 0.21 micronM in haemoglobin B sheep. Production of haemoblobin Cas a result of anaemia was confined to haemoblobin A only. The results, therefore, appear to suggest that the rise in 2,3-DPG in the red blood cells of different haemoblobin types is independent of haemoblobin C.