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Biomedical subjects

T L Holt

Publications and source records attributed to T L Holt.

At least 19 recordsLinked to original sources

Evaluation of bioelectrical impedance for prospective nutritional assessment in cystic fibrosis.

We have compared the use of bioelectrical impedance analysis (BIA) with anthropometry for the prediction of changes in total body potassium (TBK) in a group (n = 31) of children with cystic fibrosis. Linear regression analysis showed that TBK was highly correlated (r > 0.93) with height2/impedance, weight, height, and fat-free mass (FFM) estimated from skin-fold measurements. Changes in TBK were also correlated, but less well, with changes in height2/impedance, weight, height, and FFM (r = 0.69, 0.59, 0.44, and 0.40, respectively). The children were divided into two groups: those who had normal accretion of TBK (> 5%/y) and those who had suboptimal accretion of TBK (< 5%/y). Analysis of variance showed that the significant difference in the change in TBK between the groups was detectable by concomitant changes in impedance and weight but not by changes in height, FFM, or weight and height Z scores. The results of this study suggest that serial BIA measures may be useful as a predictor of progressive undernutrition and poor growth in children with cystic fibrosis.

Adolescent↗

Multiple frequency bioelectrical impedance for the prediction of total body potassium in cystic fibrosis.

The use of multiple frequency bioelectrical impedance analysis (MFBIA) was compared with single frequency bioelectrical impedance analysis (SFBIA) and anthropometry to estimate the size of the body cell mass (BCM) in a paediatric cystic fibrosis population. BCM was independently determined from the accepted gold standard reference of total body potassium (TBK). MFBIA was used to measure the impedance of the body at 248 frequencies from 4 kHz to 1 MHz. Data were analysed using Cole-Cole plots of reactance versus resistance. The limits of agreement procedure was used to determine the reliability and precision of the different techniques to predict values for TBK, in an individual subject. The results indicate that MFBIA with a precision of 12% offers little improvement over single frequency BIA but is better and more accurate than anthropometry for the prediction of TBK in an individual patient.

Journal Article↗

Nutritional rehabilitation in cystic fibrosis: a 5 year follow-up study.

Previously, we reported catch-up weight gain, growth, and improved lung function in a group of malnourished cystic fibrosis (CF) children receiving aggressive nutritional supplementation for 1 year compared with a forced expiratory volume in 1 s (FEV1)-, height-, and sex-matched comparison group receiving standard therapy. To evaluate long-term effects, the clinical progress of both groups has been studied over a 5 year period. The supplemented group (n = 10) received supplements for a median of 1.35 years to achieve nutritional rehabilitation. Compared with the nonsupplemented group (n = 14), the previously supplemented group had lower mortality (2 vs. 4, N.S.) and significantly greater weight and height z scores at 4 and 5 years. The progression of pulmonary function abnormalities as measured by FEV1 and forced vital capacity (FVC) slopes was greater at 3 years in the nonsupplemented group (FEV1, p less than 0.05) but no significant differences in rates of deterioration of pulmonary function were seen after 5 years in the two groups of survivors. We conclude that intensive nutritional support for 1 year has both short- and long-term effects on nutrition and growth, still evident some years after the cessation of this therapeutic modality. Supplementation for periods of longer than 1 year may produce greater gains and possibly prolong the improvement in pulmonary function observed in the earlier study.

Adolescent↗

Exocrine pancreatic dysfunction in malnourished Australian aboriginal children.

Pancreatic exocrine dysfunction has been frequently recorded in protein-energy malnutrition in underdeveloped countries. In addition, the pancreas requires optimal nutrition for enzyme synthesis and potentially correctable pancreatic enzyme insufficiency may play a role in the continuation of protein-energy malnutrition. This problem has not been previously evaluated in Australian Aborigines. We have applied a screening test for pancreatic dysfunction (human immunoreactive trypsinogen [IRT] assay) to the study of 398 infants (6-36 months) admitted to the Alice Springs Hospital over a 20-month period. All infants were assessed by anthropometric measures and were assigned to three nutritional groups (normal, moderate or severely malnourished) and two growth groups (stunted or not stunted). Of the 198 infants who had at least a single serum cationic trypsinogen measurement taken, normal values for serum IRT (with confidence limits) were obtained from 57 children, who were normally nourished. IRT levels were significantly correlated with the degree of underweight but there was no correlation with the degree of stunting or age. Mean IRT levels for the moderate and severely underweight groups were significantly greater than the mean for the normal group (P less than 0.01). Seventeen children (8.6%) had trypsinogen levels in excess of the 95th percentile for the normally nourished group, reflecting acinar cell damage or ductal obstruction. We conclude that pancreatic dysfunction may be a common and important overlooked factor contributing to ongoing malnutrition and disease in malnourished Australian Aboriginal children.

Anthropometry↗

Protein turnover in malnourished patients with cystic fibrosis: effects of elemental and nonelemental nutritional supplements.

To evaluate the relative efficacy of nonelemental versus semielemental enteral supplements for nutritional rehabilitation of cystic fibrosis (CF) patients, whole-body protein turnover using the [15N]glycine method was studied in nine malnourished CF patients during enteral feedings, in a block design study comparing a semielemental formula (Criticare), a higher protein density but nonelemental formula (Traumacal) (T), and a nonelemental formula that had been modified to become isocaloric and isonitrogenous to the semielemental formula (modified Traumacal, MT). No significant differences in rates of protein synthesis or catabolism were observed comparing the three formulas. However, the higher protein density nonelemental formula resulted in higher net protein deposition compared to the other two formulas (T + 0.42 g kg-1 10 h-1 versus 0.33 g kg-1 10 h-1 for Criticare and -0.59 g kg-1 10 h-1 for MT), although this was significant (p less than 0.05) for the MT versus T comparison only. This study lends support to the use of less expensive nonelemental formulas for the nutritional management of malnourished patients with CF.

Adolescent↗

Total body potassium in cystic fibrosis.

To further evaluate the nature of malnutrition, define at-risk groups, and confirm the efficacy of nutritional supplementation on body composition in cystic fibrosis (CF), we have conducted longitudinal and cross-sectional studies of total body potassium (TBK) in 161 unselected CF subjects aged 1 month to 17 years. TBK was determined by measurement of 40K in a whole body counter, reflecting body cell mass (BCM), the vital work-performing and growing cellular component of the body. Compared with normal TBK data for age and sex from pooled measurements of 1,629 healthy children aged 1 week to 17 years, CF infants (n = 12) diagnosed by newborn screening were depleted in TBK at diagnosis and showed catch-up with therapy by 1 year; CF children aged 2-17 years (n = 140) showed a tendency for inadequate accretion of TBK (and thus BCM) with increasing age, although the normal correlation between TBK and weight and height was maintained in the majority suggesting a pattern of nutritional stunting of growth; and malnourished CF children (n = 9) showed significant catch-up in TBK with long-term nutritional rehabilitation (85-98% of TBK predicted for weight and height). These studies suggest that potentially serious, but possibly correctable deficits, in the growth of the body cell mass as measured by TBK occur commonly in CF. These deficits may be established very early in life and if not corrected lead to progressive nutritional growth retardation with increasing age.

Adolescent↗

Increased energy expenditure in young children with cystic fibrosis.

To investigate the role of energy expenditure in the altered energy balance in cystic fibrosis (CF), total energy expenditure (TEE) was measured by the doubly-labelled water method in 9 clinically well CF infants (body weight 7.3-10.9 kg) without chronic lung disease. CF infants had 25% higher rates of energy expenditure when compared with data derived from measurements of TEE obtained by the same method in 16 healthy infants, matched for age and body weight. Mean TEE (SEM) for CF was 950 (38) kcal, vs 876 (72) kcal for controls matched for age and 758 (46) kcal for controls matched for weight. Although subclinical disease activity cannot be excluded as a determinant of the excess TEE, the possibility of an energy-requiring basic defect is suggested, because further analysis indicated that factors other than body weight, degree of underweight, presence of pancreatic insufficiency, or presence of lung disease were important. Increased TEE may contribute to undernutrition in CF, even in the absence of chronic lung disease.

Body Water↗

Short-term nutritional supplementation during management of pulmonary exacerbations in cystic fibrosis: a controlled study, including effects of protein turnover.

Effects of nutritional supplements on minimizing weight loss and abnormalities of protein turnover during pulmonary exacerbations in cystic fibrosis (CF) were studied by controlled trial. Patients received pulmonary therapy and either standard diet (n = 10) or adjunctive enteral supplements (n = 12). Initial protein turnover, measured by [15N]glycine kinetics, showed alterations of protein synthesis (P Syn) and catabolism (P Cat), which correlated with the degree of underweight, and negligible net protein deposition (P Dep). With treatment both groups had significant increases in mean body weight and forced expiratory volume in 1 s, expressed as percent predicted value for height (FEV1) by 3 wk, but a significant correlation between initial underweight and subsequent weight gain was observed only in supplemented patients. Mean P Syn and P Dep increased significantly (p less than 0.001) only in the supplemented group. Pulmonary exacerbations in CF have important adverse effects on body-protein metabolism, similar to changes in protein-energy malnutrition and infection. These effects are reversed by short-term nutritional support. Strategic nutritional intervention should thus be considered in management, especially in malnourished patients.

Adolescent↗

The use of a synthetic prostaglandin E1 analogue (misoprostol) as an adjunct to pancreatic enzyme replacement in cystic fibrosis.

Eleven cystic fibrosis children (mean age, 9.6 years) were chosen at random to participate in a study to observe the effects of concurrently stimulating gastric/duodenal bicarbonate secretion and inhibiting gastric acid secretion, using a methylated prostaglandin E1 analogue in patients with pancreatic insufficiency and taking pancreatic enzymes. Percentage fat absorption in 3-day stool collections were calculated before and after commencing therapy with misoprostol, 400 micrograms/day in divided doses. We found a significant reduction in fat output (14.7 +/- 11.7 versus 7.5 +/- 3.5 g/day, p less than 0.05) in the study group as a whole and a significant reduction in steatorrhoeic level as a percentage of fat intake in all of the patients with abnormal base-line collections (23.1% versus 9.2%, p less than 0.002). We conclude that misoprostol should be considered in cystic fibrosis patients with steatorrhoea as a means of improving nutrient absorption.

Alprostadil↗

Nutritional rehabilitation in cystic fibrosis: controlled studies of effects on nutritional growth retardation, body protein turnover, and course of pulmonary disease.

The effects of a sustained increase in energy and protein intake on weight gain, growth, body protein metabolism, and the course of pulmonary disease were studied in 10 undernourished patients with cystic fibrosis unable to maintain nutrition and growth by the oral route and with declining nutritional and pulmonary status in the year prior to study. A 1-year course of nutrient supplementation using a semielemental high-nitrogen formula was delivered by nocturnal intragastric feeding or as an orally administered supplement; progress was compared with that of 14 height-, sex- and FEV1-matched patients with cystic fibrosis receiving conventional therapy. Supplementation resulted in a catch-up weight gain and sustained improvement in linear growth, with fewer pulmonary infections per year than during the initial observation period. Better weight gain and linear growth than in the comparison group were observed, as well as a significant reversal of the trend for deteriorating lung function. Compared with data from healthy children, 15N-glycine kinetics demonstrated increased protein breakdown and negligible net protein deposition in the treatment group prior to supplementation. After supplementation, synthesis in excess of breakdown, with net protein accretion, occurred by 1 month of supplementation. By 6 to 12 months a significant reduction in the previously high rate of mean synthesis and breakdown was observed, with maintenance of net anabolism. These dynamic changes in whole-body protein turnover reflect a long-term improvement in energy and protein intake, which can favorably affect nutrition, growth, and the course of pulmonary disease in problem cases of cystic fibrosis.

Adolescent↗

Whole body protein turnover in malnourished cystic fibrosis patients and its relationship to pulmonary disease.

To investigate the effect of pulmonary disease in cystic fibrosis (CF), total body protein synthesis and catabolism were determined in eight CF children with acute exacerbations of pulmonary infection at the time of study (CF I), a group of CF children (n = 7) with chronic but stable pulmonary disease (CF II) and a group (n = 8) of healthy children. Protein synthesis was determined by the method of Waterlow et al (1978) using a single oral dose of 15N glycine and protein catabolism derived from nitrogen balance. Protein synthesis was markedly decreased (p less than 0.001) in the CF I group (1.01 +/- 0.10 g kg-1 10 h-1) compared with that of controls (2.02 +/- 0.08) and with CF children with chronic but stable pulmonary disease (CF II) (2.36 +/- 0.17). Protein catabolism was increased (p less than 0.01) in the CF II group compared with both controls and CF I. These findings contrast strongly to studies in normal children and those with mild protein-energy malnutrition (PEM) and infection, where infection increased protein synthesis, but are consistent with the observed decrease in protein turnover where severe PEM is accompanied by infection. We conclude that repeated pulmonary infection can adversely affect protein-energy balance and that adequate nutritional support should be considered in management during and after each episode.

Adolescent↗

Longitudinal study of the body composition of weight gain in exclusively breast-fed and intake-measured whey-based formula-fed infants to age 3 months.

Body composition and the composition of weight gain in 82 healthy infants during the first 3 months of life were measured in relation to the type of feeding and nutrient intakes by serial measurements of total body potassium (TBK), anthropometry, and formula intake. Infants were exclusively fed either breast milk (n = 34, B fed) or whey-based formula (n = 48, F fed). Formula intakes were substantially lower than WHO-FAO recommendations (although serial weights paralleled standards), and were significantly greater in male infants, who had greater gains in weight and lean tissue than females. In both sexes, tissues low in K (fat and extracellular water) were added faster to the body weight than lean tissue. Overall, compared with B fed infants, F fed infants gained less weight between birth and 10 days and more weight between 10 and 90 days, although mean actual weights at 90 days were similar; formula feeding caused greater fat deposition in males and greater daily gains in lean mass in females. Differences in both quantity and quality of ingested nutrients account for these differences although the biological importance of these findings is speculative. These studies further elucidate the nature of growth in relation to modern feeding practices and the question of optimal versus maximal nutrient intake and growth in early life.

Anthropometry↗

Leucine metabolism and body cell mass in cystic fibrosis.

To further investigate the nature of malnutrition in cystic fibrosis (CF), specifically to evaluate the influence of body composition on leucine metabolism and determine whether measures used as reference standards alter comparative differences in protein metabolism, we measured [13C]leucine kinetics in nine well-nourished and eight malnourished, height-, FEV1-, and sex-matched CF subjects. Body cell mass was measured by total-body potassium (K40) analysis. Leucine turnover did not significantly differ between groups in absolute values or when corrected for body weight, body height, or surface area. However, malnourished CF patients had accelerated leucine turnover based on body cell mass measurements. Mean leucine synthesis per unit body cell mass in the malnourished group was 147% higher than that of the well-nourished group (p < 0.001). These data indicate that altered body composition is an important factor influencing protein metabolism in CF and should be considered in future metabolic studies. The importance of potentially serious but possibly correctable deficits in body cell mass in CF is emphasized.

Adolescent↗