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Biomedical subjects

K J Gaskin

Publications and source records attributed to K J Gaskin.

65 records · Page 4Linked to original sources

Colipase and lipase secretion in childhood-onset pancreatic insufficiency. Delineation of patients with steatorrhea secondary to relative colipase deficiency.

Pancreatic lipase and colipase secretion was assessed in 64 patients with pancreatic disease, 24 of whom had steatorrhea, and in 14 control subjects. A wide range of lipase and colipase secretion was seen in patients both with and without steatorrhea. Considerable loss of pancreatic lipase and colipase secretion had to occur before steatorrhea developed, as the highest hourly secretion of lipase and colipase in this group of patients was less than 4% and less than 2%, respectively, of the lowest values recorded in normal subjects. Colipase and lipase outputs were very strongly correlated (r = 0.96) throughout the range of pancreatic function. Lipase was always unsaturated with respect to colipase, but in only a limited number of patients with relatively low pancreatic secretion was the degree of unsaturation greater than 2 standard deviations below the mean. The importance of low saturation or low colipase secretion was evident in a group of 11 patients with a narrow range of lipase secretion in a transitional zone between secretion rates associated with steatorrhea and with normal fat excretion. In this group, 7 patients were identified in whom colipase deficiency appeared to be the sole cause of steatorrhea. The correlation of colipase secretion with the level of fecal fat excretion was highly significant (p less than 0.001) and indicated that fat digestion and subsequent fat absorption depended on colipase secretion up to at least a level of 25% fecal fat excretion. Nonpancreatic factors could well govern the extent of fat absorption above this level, as colipase secretory values in this range were uniformly low.

Adolescent↗

Plasma immunoreactive anionic pancreatic trypsin in cystic fibrosis.

Previous data from this laboratory have shown good correlation between plasma cationic trypsin(ogen) and levels of pancreatic function in older cystic fibrosis (CF) patients with and without malabsorption. In the present study a radioimmunoassay for human anionic trypsin(ogen) has been employed in the assessment of pancreatic function in older patients with CF. Immunoreactive anionic trypsin(ogen) levels correlated poorly with pancreatic function due to an apparent elevation of this enzyme in many older CF patients with malabsorption (CF + M). When plasma from three older CF + M patients is examined for the molecular size of the apparent immunoreactive material detected, no free anionic trypsinogen is observed. Instead, a broad peak of apparent immunoreactive material appears in the gammaglobulin region. However, only free anionic trypsinogen could be detected in plasma from two CF patients without malabsorption (CF - M), who had not received pancreatic enzyme supplements. It appears possible that a human plasma immunoglobulin G (IgG) to porcine pancreatic enzyme in the CF + M patients might interfere in the assay by binding TLCK--anionic trypsin tracer. It is unclear why such an effect does not appear to occur in the cationic trypsin(ogen) assay. The results of the current study suggest that, for assessment of pancreatic insufficiency in CF, the radioimmunoassay for cationic trypsin(ogen) is more useful than the presently available radioimmunoassay for the anionic form.

Adolescent↗

Colipase and maximally activated pancreatic lipase in normal subjects and patients with steatorrhea.

Human pancreatic lipase in duodenal secretions was studied under conditions of maximal activation by porcine colipase and maximal inhibition by sodium taurodeoxycholate. In almost all samples, total lipase activity in 4 mM sodium taurodeoxycholate was activated by the addition of porcine colipase. Activation was linear until saturation by cofactor was reached, and maximum activity was greater than that obtained in the absence of bile salts. At pH 8.0 in 4 mM sodium taurodeoxycholate, lipase activity was due to pancreatic lipase in samples from normal and steatorrheic individuals and was proportional to the concentration of endogenous colipase in samples that could be activated by exogenous colipase. In these samples, therefore, colipase activity could be conveniently assayed as the lipase activity at pH 0.8 in 4 mM sodium taurodeoxycholate. Colipase to total pancreatic lipase ratios varied widely from individual to individual and on average were significantly lower in steatorrheic patients. In individual samples, colipase secretion was stimulated by pancreozymin and secretin roughly in parallel with total pancreatic lipase, but some variation in the ratio of the two was often seen in successive collection periods. Because pancreatic lipase is usually unsaturated with respect to cofactor, lipolytic activity in duodenal secretions may be finely controlled by modulation of colipase secretion.

Animals↗

Steatorrhea and pancreatic insufficiency in Shwachman syndrome.

Fat absorption was assessed on two or more occasions in 12 of 14 patients with Shwachman syndrome. Of 11 children who initially had steatorrhea, 6 were subsequently found to have normal fat excretion. In 10 of these 11 patients the last estimate was smaller than the initial estimate after an interval of 0.3-12.7 yr. The most dramatic improvement occurred under 4 yr of age but improvement appeared to continue over a more extended period where sufficient follow-up was available. All patients had pronounced pancreatic insufficiency as tested by duodenal drainage corrected by nonabsorbable marker under stimulation with cholecystokinin and secretin. Pancreatic lipase secretion was assessed in 3 patients with steatorrhea and 5 without steatorrhea (73% of the surviving patients) using a sensitive assay which used maximum stimulation with colipase. Pancreatic lipase secretion was less than 2% of normal mean secretion in the steatorrheic patients and ranged from 3.7% to 13.6% in the patients without steatorrhea. These results indicate that fat absorption improves in the majority of patients with Shwachman syndrome and appears to be associated with marginal improvement in pancreatic lipase secretion. Due to the occult nature of bowel complaints in older patients, the diagnosis may be overlooked unless careful screening for pancreatic function takes place.

Adolescent↗

Plasma immunoreactive pancreatic cationic trypsinogen in cystic fibrosis: a sensitive indicator of exocrine pancreatic dysfunction.

Plasma immunoreactive cationic trypsin(ogen) levels were determined in 32 control subjects and 43 patients with varying degrees of pancreatic insufficiency including 35 with cystic fibrosis (CF) and eight with Shwachman's syndrome. In six CF infants less than 2 years of age, plasma trypsin(ogen) levels were significantly elevated (97.3 +/- 62.2 ng/ml) above the normal range for nine controls (7.0 +/- 5.9 ng/ml; P less than 0.025). Four of these infants had steatorrhea, three of whom had undetectable duodenal trypsin activity after stimulation with secretin-cholecystokinin. In two CF infants, molecular size fractionation by gel filtration of plasma followed by radioimmunoassay of the column fractions demonstrated that trypsinogen was the only immunoreactive species in the circulation. In contrast, in older CF patients with steatorrhea (mean age, 15.3 +/- 4.6 years), plasma cationic trypsin(ogen) levels were undetectable or low (1.1 +/- 1.7 ng/ml). This finding clearly distinguished them from older CF patients without steatorrhea (mean age, 14.3 +/- 3.9 years) in whom cationic trypsin(ogen) levels were significantly higher (23.3 +/- 17.6 ng/ml; P less than 0.01). The mean trypsin(ogen) concentration in the older CF patients without steatorrhea did not differ from the mean value for 23 normal subjects of similar age. Plasma cationic trypsin(ogen) levels in two Schwachman's patients with steatorrhea (0.19 and 0.86 ng/ml) were significantly lower than the values found in six Shwachman's patients without steatorrhea (5.9 +/- 2.3 ng/ml; P less than 0.025). Furthermore, in nine older CF patients and eight Schwachman's patients, circulating trypsin(ogen) levels were highly correlated with duodenal trypsin output after secretin-cholecystokinin stimulation (r = 0.946, P less than 0.01; r = 0.899, P less than 0.01, respectively). These results suggest that in CF infants high levels of circulating trypsin(ogen) persist even in those with Shwachman's syndrome, however, circulating trypsin(ogen) accurately reflects residual pancreatic function.

Adolescent↗

The use of body mass index to predict body composition in children.

BACKGROUND: Simple anthropometric indices of body composition have particular appeal for use in children, and as such body mass index (BMI) has been used to predict percentage body fat in a number of studies. AIM: To evaluate the relationship between BMI and percentage body fat (%body fat) and a proposed, more appropriate relationship between BMI and fat mass/height(2) in a cohort of young children. SUBJECTS AND METHODS: Cross-sectional study of 109 children aged between 6 and 10 years residing in either Sydney or Brisbane, Australia. Weight and height were measured using standard methods. Body composition was measured using a stable isotope method to firstly determine total body water and subsequently fat free mass. RESULTS: The correlation between BMI and fat mass/height(2) was markedly greater than that between BMI and percentage body fat. In the entire group of children the R(2) (x100%) value for the relationship between BMI and fat mass/height(2) was 73.3% compared with 46.5% for the relationship between BMI and percentage body fat. CONCLUSIONS: We have shown that the use of BMI to predict fat mass/height(2), and consequently percentage body fat, is superior to the use of BMI to predict percentage body fat based directly upon the R(2) values of the above analysis.

Anthropometry↗