Disaccharidase activities in small intestinal mucosa in patients with cystic fibrosis.

The disaccharidase activities in small intestinal biopsies were related to the morphology of the mucosa and the ages of 63 patients with cystic fibrosis and 177 healthy control subjects of Caucasian origin. In patients with CF and in the healthy control subjects under 5 years of age with normal intestinal mucosa, no low lactase activity was found. In those patients with CF who were over 5 years of age, one group had high and one group had low lactase activity, as occurs in healthy Caucasian control subjects of the same age. This finding supports the view that in patients with CF, lactase deficiency is not related to the disease entity. In patients with or without CF who had the same degree of mucosal atrophy, the decrease of disaccharidase activities followed the same pattern, indicating that enzyme activities are affected to the same extent by the damage of the mucosa. In patients with CF with pancreatic insufficiency, the disaccharidase activities were significantly (P less than 0.001) higher when compared to those in control subjects of the same age and ethnic group, although the increase was not uniform in all patients with cystic fibrosis.     

Serum zinc in small children with coeliac disease

In coeliac disease (CD) there is a gluten-induced small bowel enteropathy leading to malabsorption of various nutrients, vitamins and trace elements. Low levels of serum zinc have been reported in adults with untreated CD. In the present study we related the serum concentration of zinc to the morphology of the small bowel mucosa in 58 children, all under 4 years of age and under investigation for coeliac disease. The mean serum concentration of zinc (mean ± SD; μmol/L) was significantly lower in children with untreated CD (9.7 ± 2.0) (n = 11) compared to non-coeliac children without enteropathy (15.1 ± 2.3) (n = 16) (p < 0.001), coeliac children on a gluten-free diet without enteropathy (14.2 ± 1.6) (n = 14) (p < 0.001), coeliac children on gluten challenge with enteropathy (14.1 ± 2.1) (n = 12) (p < 0.001) and coeliac children on gluten challenge without enteropathy (13.8 ± 1.9) (n = 6) (p < 0.005).
Conclusion: Serum zinc concentration is decreased in untreated coeliac children with enteropathy and normalizes on gluten-free diet. A low serum zinc value in a child being investigated for possible CD on clinical grounds can thus be used as a complementary marker for enteropathy indicating further investigation with small bowel biopsy. The hypothetical role of zinc in the pathogenesis of CD is discussed.     

Relation between pancreatic lipase activity and gastric emptying rate in children with cystic fibrosis

OBJECTIVE: To determine whether abnormal gastric emptying is responsible for the inability of pancreatic enzyme replacement therapy (PERT) to normalize fat digestion in patients with cystic fibrosis (CF) who are pancreatic-insufficient.Study design Gastric emptying of a solid meal and pancreatic lipase function were assessed in 10 children with CF and 12 healthy control subjects with noninvasive breath tests using (13)C-octanoic acid and (13)C-mixed triglyceride, respectively. Lipase function was assessed in the subjects with CF with and without PERT. RESULTS: Without PERT, the lipase activity for the patients was less than that for the control subjects (P<.001); however, with PERT, 40% of the patients had a normalized lipase function. There were no differences between the mean gastric emptying rates of the patients with CF and the control subjects (P>.05), but there was a negative correlation between gastric half emptying time and percentage improvement in (13)C-mixed triglyceride results of the patients with CF with pancreatic enzymes compared with placebo (P<.05), with patients with slow gastric emptying having less improvement with PERT. CONCLUSIONS: The success of PERT in improving pancreatic lipase activity is reduced in patients with slow gastric emptying, which could explain the variations in improvement of fat digestion with enzyme supplementation.     

Intestinal retinol esterification and serum retinol in children with cystic fibrosis

Children with cystic fibrosis (CF) often have a poor vitamin A status. We found in the present work a reduced level of serum retinol in older children with this disease. As retinol enters intestinal lymph as retinyl esters, the enzyme acyl-CoA:retinol acyltransferase (ARAT) may be of importance for retinol absorption. We have assayed ARAT activity in duodenal mucosal homogenate from children with CF. There was a large variation within the group. However, mean ARAT activity was not significantly decreased, as compared with controls. Thus, the lack of pancreatic enzymes probably is the main reason for reduced vitamin A absorption in CF. In celiac disease and in lactose intolerance--both mucosal disorders--a significant reduction of mean ARAT activity was found.     

Intestinal Dipeptide Hydrolase Activities in Undernourished Children

Intestinal dipeptide hydrolase enzymes cleave dipeptides into amino acids. In 8 undernourished children with diarrhoea, mean intestinal mucosal glyclyl-proline hydrolase activity was reduced 40%, valyl-proline hydrolase activity 38%, and alkaline phosphatase activity 54%, as compared with 4 controls. The use of hydrolysed proteins or simple amino acid mixtures in the initial treatment of undernourished children is suggested.     

Disturbed fat absorption following infectious gastroenteritis in children.

Fat absorption was studied in 10 patients recovering from an episode of acute infectious gastroenteritis who failed to gain weight despite adequate caloric intake. Three patients restudied after clinical improvement and three other infants with failure to thrive, unrelated to gastrointestinal problems, served as control subjects. Fat balance studies during the ingestion of a formula containing long-chain fatty acids demonstrated significant degrees of steatorrhea in patients (mean CFA 70.6 +/- 10.7 compared to 90.3 +/- 2.4 in control subjects). The administration of a test meal demonstrated a marked deficiency of duodenal bile acid concentration and of fat incorporation into the micellar phase in patients. Fecal bile acid excretion was significantly increased in patients (mean 33.9 +/- 11.6 microM/kg/day) as compared to control subjects (mean 13.5 +/- 3.1 microM/kg/day). Bacterial overgrowth and abnormalities of the small intestinal mucosa were not constant. Ileal dysfunction and associated bile acid loss are possible causes of disturbed fat assimilation following acute intestinal infection in children.     

Dietary intake of healthy children with cystic fibrosis compared with normal control children.

Because a low calorie intake may result in growth failure and malnutrition in patients with cystic fibrosis (CF), the dietary and energy intakes of 22 children with CF who had mild lung disease and excellent Shwachman scores were examined and compared with those of 23 normal control subjects similar in age (5 to 10 years), gender, and weight. The children with CF consumed significantly more calories than the control subjects. Calorie intake was 111 +/- 19.9% (mean +/- SD) of estimated requirements (World Health Organization recommendations) for the CF group and 97 +/- 18.7% for the control group (P = .014). Calories consumed per kilogram of body weight were 117% of World Health Organization (CF) vs 97% (control) (P = .009). Calorie intake compared to the 1989 Recommended Dietary Allowance was 106 +/- 20.6% for the CF group vs 93 +/- 19.1% for the control group. Fat consumed as a percent of total calories was similar: 33.5% (CF) vs 32.2% (control). All children with CF had pancreatic insufficiency and, on average, consumed a large number of pancreatic enzyme supplements, resulting in dietary fat absorption of 86 +/- 12%. It is concluded that these children with CF were able to maintain normal growth and energy stores on a diet that was relatively high in calories compared to control subjects and moderate in percent fat, along with an aggressive pancreatic enzyme supplement regimen.     

Hepatic damage in gluten sensitive enteropathy

Background: Gluten sensitive enteropathy has been reported to occur concomitantly with liver abnormalities, such as primary biliary cirrhosis, chronic active hepatitis and primary sclerosing cholangitis. Methods: Duodenal biopsy was performed in nine children (all with short stature, five with chronic diarrhea and three with hepatosplenomegaly of unknown etiology) with a possible diagnosis of gluten sensitive enteropathy. All of the patients had different abnormalities in serum aminotransferase levels. With the help of laboratory investigations, viral, autoimmune, metabolic and toxic etiologies which cause hepatic damage were excluded. Liver biopsy was performed in five of these patients, two showing fibrosis and three non-specific reactive changes. Gliadin antibodies were measured in six cases. Results: Intestinal mucosal histopathology was compatible with gluten sensitive enteropathy in all patients. While immunoglobulin (Ig) G gliadin antibodies were positive in all cases, only three cases were found to have positive IgA gliadin antibodies. After a gluten-free diet, levels of transaminases fell to normal within 3 months and remained so in seven of these patients. A second intestinal biopsy, which was performed after 1 year of gluten-free diet revealed normal intestinal mucosa in all patients. Conclusion: Gluten sensitive enteropathy should be considered when evaluating a child with elevated levels of serum transaminase and in cases with cryptogenic liver disease.     

Normal bone mineral density in cystic fibrosis.

BACKGROUND: Osteoporosis has been reported as a complication of cystic fibrosis (CF). AIMS: To measure bone mineral density (BMD) in non-acutely ill adults and bone mineral content (BMC) in children with CF. METHODS: We analysed data from 28 adults and 13 children with CF. Corticosteroid use was minimal for the year prior to study in both groups. Dual x ray absorptiometry was used to measure total body and regional bone mineral density in adults. In children, whole body BMC was measured. Lean tissue mass (LTM) was also measured in all subjects. There were two control groups: A (matched for LTM and height, in addition to age and gender); and B (matched for age and gender only). RESULTS: There was no difference in whole body or regional BMD density between adult CF patients and control A subjects. Both whole body and regional BMD were significantly lower in adult CF patients than in control B subjects. Total body BMD was correlated with body mass index, LTM, and percent fat in both CF and control subjects. There was no significant correlation between total body BMD or regional BMD and either NIH clinical status scores, or pulmonary function tests in adults. There was no difference in total body BMC between CF children and control A subjects. Total body BMC was significantly lower in CF children than in control B subjects. There was no correlation between pulmonary function results and BMC in children. CONCLUSION: Osteopenia and osteoporosis in CF may be caused more by malnutrition and chronic use of intravenous or oral corticosteroids than by a CF related inherent defect in BMD. Appropriate "normal" data should be selected when determining whether or not osteoporosis is present in a CF patient.     

Trimebutine-induced phase III-like activity in infants with intestinal motility disorders

Duodenal manometric recordings were performed in five male children (mean age 11.7 +/- 6.8 months) suffering from severe digestive pathology with clinical findings of dysmotility; they required total parenteral nutrition: one case of enteropathy following intestinal resection for congenital small bowel atresia, and four cases of intestinal pseudoobstruction. The basal 3-h fasting recordings showed complete disorganization of interdigestive activity characterized by an absence of migrating motor complexes and a marked basal hypomotility with motor indices lower than in control subjects. Intravenous trimebutine (3 mg/kg) produced a phase III-like activity 88 +/- 121 s after administration in four cases. The activity lasted 236 +/- 105 s and had a mean frequency of 11.75 +/- 0.86 waves/min. It was propagated aborally in the two patients having two duodenal recording sites. Trimebutine-induced phase III activity was followed by signs of peristalsis in two patients.     

Calcium and sodium transport processes in patients with cystic fibrosis. I. A specific decrease in Mg2+-dependent, Ca2+-adenosine triphosphatase activity in erythrocyte membranes from cystic fibrosis patients.

Calcium-ATPase activity (Mg2+-dependent Ca2+-ATPase, ATP phosphohydrolase, EC 3.6.1.3) in erythrocyte membrane preparations from cystic fibrosis (CF) patients was greatly reduced compared to erythrocyte membranes from control subjects. The Km for calcium was found to be similar in the two groups; however, the Vmax, the maximal rate of activation of the Ca2+-ATPase, is reduced by 50% in the erythrocyte membrane preparations of the CF patients (P less than 0.001). In contrast, the Mg2+-ATPase activity of erythrocyte membranes from CF patients was unchanged compared to the control subjects. No difference in the Na+,K+-ATPase activity in erythrocyte membranes from CF patients compared to control patients could be observed. This indicates that the Ca2+-ATPase activity noted in CF erythrocytes is not part of a generalized membrane or membrane-bound enzyme alteration. It remains to be determined whether this alteration in Ca2+-ATPase activity is directly related to a defect in calcium transport in these cells and is a generalized phenomenon in CF present in cell types more directly involved in secretion.     

Normal bone mineral density in cystic fibrosis

BACKGROUND—Osteoporosis has been reported as a complication of cystic fibrosis (CF).AIMS—To measure bone mineral density (BMD) in non-acutely ill adults and bone mineral content (BMC) in children with CF.METHODS—We analysed data from 28 adults and 13 children with CF. Corticosteroid use was minimal for the year prior to study in both groups. Dual x ray absorptiometry was used to measure total body and regional bone mineral density in adults. In children, whole body BMC was measured. Lean tissue mass (LTM) was also measured in all subjects. There were two control groups: A (matched for LTM and height, in addition to age and gender); and B (matched for age and gender only).RESULTS—There was no difference in whole body or regional BMD density between adult CF patients and control A subjects. Both whole body and regional BMD were significantly lower in adult CF patients than in control B subjects. Total body BMD was correlated with body mass index, LTM, and percent fat in both CF and control subjects. There was no significant correlation between total body BMD or regional BMD and either NIH clinical status scores, or pulmonary function tests in adults. There was no difference in total body BMC between CF children and control A subjects. Total body BMC was significantly lower in CF children than in control B subjects. There was no correlation between pulmonary function results and BMC in children.CONCLUSION—Osteopenia and osteoporosis in CF may be caused more by malnutrition and chronic use of intravenous or oral corticosteroids than by a CF related inherent defect in BMD. Appropriate "normal" data should be selected when determining whether or not osteoporosis is present in a CF patient.     

Lactulose-rhamnose intestinal permeability in children with cystic fibrosis

The lactulose-rhamnose intestinal permeability test was performed in 10 cystic fibrosis (CF) children. Urine was collected for 5 h after oral intake of the test solution. A single thin-layer chromatography followed by densitometry was used for the measurement of lactulose and rhamnose concentrations in the urine specimens. The excretion of each molecule was expressed as the percentage of the orally administered dose excreted and the lactulose-rhamnose ratio was the ratio of the percentage quantities of each probe molecule excreted. The mean lactulose-rhamnose excretion ratio in CF patients and controls was 0.16 and 0.038, respectively (p less than 0.001). The mean 5-h lactulose excretion was 2% and 0.28% in CF patients and control subjects, respectively (p less than 0.001). The mean 5-h rhamnose excretion was 12.8% and 7.6% in CF patients and control subjects (p less than 0.05). We conclude that CF patients have an increased intestinal permeability to lactulose and rhamnose. Further studies are needed in order to elucidate the mechanisms involved as well as the eventual nutritional implications.     

Feeding behavior problems in children with cystic fibrosis in the UK: prevalence and comparison with healthy controls

BACKGROUND: Feeding behavior problems contribute to inadequate dietary intake for many patients with cystic fibrosis (CF). However, to establish effective intervention programs, more needs to be known about the occurrence and distribution of these difficulties. The aims of this study were to establish the prevalence and range of disruptive child behaviors (DCB) in patients with CF and the inappropriate parental responses (IPR) during mealtimes and to compare the results with those of healthy children. METHODS: In study A, parents of 108 patients (aged 1-7 years) completed a Behavioural Paediatric Feeding Assessment Scale comprising two domains: DCBs and IPRs during mealtimes. Parents rated the frequency of the behaviors and responses and identified those they considered problematic. In study B, data from the CF group (n = 69, aged 1-12 years) were compared with 69 age- and sex-matched control subjects. RESULTS: Parents of children with CF aged 5 to 8 years recorded significantly more DCBs than those in all other age ranges. These parents also reported significantly more IPRs than did parents of children aged 9 to 12 years and 13 to 17 years. Parents of children with CF reported significantly more DCBs and IPRs than did those of the control subjects. There were significantly more problematic DCBs and IPRs in the CF group than in the control group for children aged 5 to 8 years and 9 to 12 years but not for those aged 1 to 4 years. CONCLUSIONS: Parents of children with CF report more feeding behavior problems than do those of healthy control subjects. The high prevalence of feeding behavior problems in older children suggests that preventative and reactive interventions must continue throughout childhood and vary according to the child's developmental abilities.     

Serum glutathione reductase and cystic fibrosis.

Serum glutathione reductase (NADPH-GSSG oxidoreductase, EC. 1.6.4.2 (GR)) has been examined in cystic fibrosis subjects (CF), obligate CF heterozygotes, and control subjects. Serum protein concentration was similar in the three groups. Regardless of the units used to express activity (milligrams of protein or milliters of serum) or whether or not samples were dialyzed against water or phosphate buffer, mean serum GR in CF was greater than in control subjects (P less than or equal to 0.002) in all series over several years. Under the above assay conditions no difference in serum GR between control subjects and carriers was detected. Calculated and assayed values of combined control and CF sera agreed as did expected and observed 50% activity in 1:2 sera dilutions in CF, control subjects, and carriers. Addition of FAD to incubation media did not effect enzyme activity in the three groups. Differences between CF and control subjects persisted after dialysis in membranes permitting passage of molecules of approximately 12,000 mol wt or less. These findings would tend to exclude the effect of extraneous serum factors in explaining the diffferences between CF and control subjects. The percentage of initial GR activity after four days storage (0-4 degrees) was significantly greater in CF than in control subjects (P less than 0.025). The effect of heparin on serum GR was recorded as the percentage of activity after incubation with heparin vs. activity in the standard assay for individual subjects. The effect of incubation with 5 mug/ml heparin on serum GR activity was greater in control subjects than in carriers (P less than 0.0005) and CF (P less than 0.0005). Mean serum GR activity in CF and carriers was unaffected by heparin, whereas mean activity in control subjects was decreased. In no control was the percentage of initial activity with heparin greater than the mean of CF and carrier groups. Only 3 of 20 CF and 4 of 20 carrier individuals had percentages lower than the control mean. The CF and carrier distributions were clearly different from the control distribution. Serum GR was determined in seven non-CF individuals with chronic obstructive pulmonary disease (COPD). Activity in the COPD was different from CF and no different from control subjects. In none of these controls or COPD was serum GR as great as the CF mean. Serum GR in no CF was as low as the mean of control subjects or COPD. It is concluded that serum GR activity is greater in CF than in control subjects, carriers, and non-CF COPD subjects; that the difference in activity is not attributable to an extraneous serum factor, that the activity difference is not secondary to chronic respiratory disease; that in comparison with control subjects, GR from CF serum behaves differently after storage; and that serum GR from CF and carriers behaves differently from control GR in the presence of heparin.     

Bile acid malabsorption in cystic fibrosis with and without pancreatic insufficiency

Serum conjugated cholic acid (CCA) and conjugated chenodeoxycholic acid (CCDCA) fasting levels were measured in 30 children with cystic fibrosis (CF) without liver involvement, and mean levels were not significantly different from control values. In seven children (four with partially corrected pancreatic insufficiency and three without pancreatic insufficiency) serum levels of both primary bile acids (BAs) were also measured after the ingestion of a standard liquid meal; the values were then compared with those for total and fractional fecal BA excretion. The CCA mean peak increase was significantly reduced in patients with pancreatic insufficiency (p less than 0.01), as well as in those without pancreatic insufficiency (p less than 0.05), as compared to controls. The CCDCA mean peak increase was reduced only in patients with pancreatic insufficiency (p less than 0.01). Fecal results confirmed serum data, showing a significantly increased excretion of cholic and deoxycholic acids in patients without pancreatic insufficiency as compared to controls (p less than 0.02), despite a similar total BA excretion. In patients with pancreatic insufficiency, total fecal BA levels were markedly increased compared to control values (p less than 0.001); the fecal percentage of chenodeoxycholic and lithocholic acids was greater than that recorded in patients without pancreatic insufficiency (p less than 0.05), in agreement with the different behaviour of serum CCDCA postprandial curves for the two groups of patients. The results are consistent with selective malabsorption of cholic acid in CF, independent of the presence of pancreatic insufficiency; they confirm the usefulness of serum BA postprandial determinations in measuring BA malabsorption.     

Abnormalities of intestinal permeability of 51Cr-EDTA in mucoviscidosis

Intestinal permeability to 51Cr-EDTA was studied in 20 children with cystic fibrosis (CF) and a mean age of 10.7 years, in 7 control adults and in 11 control children. 51Cr-EDTA urinary excretion (mean +/- SD) expressed as a percentage of the orally administered activity was: control children: 1.59 +/- 0.55%, control adults: 1.47 +/- 0.62%, CF patients: 10.7 +/- 8.6%. The difference between CF patients and control children on one hand, between CF patients and control adults on the other hand, was statistically significant (p less than 0.001). Only 3 CF patients had values within the limits of those observed in controls. A statistically significant correlation (p less than 0.01) was observed between the 51Cr-EDTA urinary excretion and steatorrhea. No correlation was found between 51Cr-EDTA urinary excretion and the following parameters: age, sex, weight, height, Shwachman score, liver cirrhosis, oral administration of a mucolytic agent. The eventual, especially nutritional, consequences of this increase of the intestinal permeability in the course of CF remain to be clarified.     

Bone status in cystic fibrosis.

AIM: To investigate bone mineral status of children with cystic fibrosis (CF). METHODS: In 29 children with CF and 49 matched controls, bone mineral content (BMC), projected bone area (BA), and areal bone mineral density (BMD) of the whole body, total hip, and lumbar spine (L1-L4) were measured using dual energy x ray absorptiometry. The BMC values at each site were adjusted for BA, height, and weight. At the lumbar spine, the bone mineral apparent density (BMAD) was calculated by dividing the BMC by the estimated volume, derived from BA. Vertebral (T12-L3) trabecular bone mineral density (vTBMD) was measured using quantitative computed tomography in children with CF. Calcaneal broadband ultrasound attenuation (BUA) was measured in CF patients and controls using quantitative ultrasound. The disease severity of CF children was evaluated by the Shwachman-Kulczycki (SK) score. RESULTS: The mean BUA, whole body and regional BA, adjusted BMC, and areal BMD of children with CF were not different from those of controls. The mean BMAD of the lumbar spine was reduced in CF patients compared with controls, whereas the mean vTBMD standard deviation scores were significantly higher in CF patients. The median SK score of the CF group was 81 (range 42-100), indicating that as a group our CF patient population had relatively mild disease. CONCLUSION: The normal vertebral BMC, decreased BMAD, and higher vTBMD suggests that the vertebral cortical thickness or density might be reduced in CF subjects. The overall bone mineral status of CF children with relatively mild disease was not different from size matched controls.     

Bone status in cystic fibrosis

AIM—To investigate bone mineral status of children with cystic fibrosis (CF).METHODS—In 29 children with CF and 49 matched controls, bone mineral content (BMC), projected bone area (BA), and areal bone mineral density (BMD) of the whole body, total hip, and lumbar spine (L1-L4) were measured using dual energy x ray absorptiometry. The BMC values at each site were adjusted for BA, height, and weight. At the lumbar spine, the bone mineral apparent density (BMAD) was calculated by dividing the BMC by the estimated volume, derived from BA. Vertebral (T12-L3) trabecular bone mineral density (vTBMD) was measured using quantitative computed tomography in children with CF. Calcaneal broadband ultrasound attenuation (BUA) was measured in CF patients and controls using quantitative ultrasound. The disease severity of CF children was evaluated by the Shwachman-Kulczycki (SK) score.RESULTS—The mean BUA, whole body and regional BA, adjusted BMC, and areal BMD of children with CF were not different from those of controls. The mean BMAD of the lumbar spine was reduced in CF patients compared with controls, whereas the mean vTBMD standard deviation scores were significantly higher in CF patients. The median SK score of the CF group was 81 (range 42-100), indicating that as a group our CF patient population had relatively mild disease.CONCLUSION—The normal vertebral BMC, decreased BMAD, and higher vTBMD suggests that the vertebral cortical thickness or density might be reduced in CF subjects. The overall bone mineral status of CF children with relatively mild disease was not different from size matched controls.     

Assessment of obesity status in outpatients from three disease states

Aim: To assess obesity status in patients with cystic fibrosis (CF), human immunodeficiency virus (HIV) and various metabolic disorders (MD), through comparison against a) UK reference data and b) contemporary healthy children. Methods: Weight, height, waist circumference (WC), and triceps (TRI) and sub-scapular (SUBS) skinfold thickness were measured in a total of 57 healthy, 49 HIV, 68 MD and 49 CF children. Using published reference data, standard deviation scores (SDS) were calculated. Results: CF patients had weight, height and BMI SDS significantly below zero. MD patients had height SDS significantly below, and BMI SDS significantly above, zero. Healthy children had BMI SDS significantly above zero. In all three patient groups and healthy children, TRI and WC SDS were significantly above zero. SUBS SDS was also significantly above zero in patients with MD and HIV. WC SDS was greater in patients than in healthy children, but only significantly so for the MD children.

Conclusion: In all three patient groups, even those associated with reduced stature or reduced weight, indices of fatness were significantly increased relative to reference data. The tendency to central fatness was evident in healthy children, but was more extreme in patients, especially those with MD.