The treatment of malabsorption in cystic fibrosis with pancreatic extracts and inhibition of gastric acidity by antacids and cimetidine.
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Biomedical subjects
Publications and source records attributed to R B Elliott.
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Cold-reacting serum lymphocytotoxic antibodies (LCAs) were measured in sera from 230 insulin-dependent juvenile-onset diabetes mellitus (IDDM) patients and from 116 control subjects. LCAs were present in only 4% of control sera compared with 19% in IDDM patients. The most significant determinant of LCAs was time since onset of diabetes; within the first 12 mo, 55% of IDDM sera had LCAs, compared with 25% after one year and 15% after five years of diabetes. LCAs were absent in sera from patients with IDDM for 10 yr or more. Genetic factors were also implicated in susceptibility toi occurrence of LCAs. HLA antigen B8 and B18 were associated with an increased risk for LCAs, whereas HLA-B7 was associated with a decreased risk. The relative risk for LCAs in patients positive for HLA-B8 but not B7 was 2.3, compared with 0.0 in HLA-B7/B8 heterozygotes. In contrast, B7 did not provide protection from LCAs in B18/B7 IDDM patients. Properdin factor B (Bf) alleles, which are in linkage disequilibrium with alleles of the HLA-B locus, were also associated with LCAs, IDDM patients with alleles BfS1 or BfF hd a prevalence of LCAs of 7%, significantly less than the 39% in Bf-F1S or -F1 patients. LCAs were not identical or closely correlated to pancreatic islet cell antibodies. Our findings indicate genetic heterogeneity in, yet, another autoimmune process in IDDM.
Children suffer excessive morbidity and mortality from traffic accidents in New Zealand. Pedestrian and bicycle accidents constitute one-third of these accidents. The pattern of involvement of children in such incidents may suggest specific preventive measures.
A cross-over trial was conducted on 10 children with moderate to severe asthma, who had positive skin tests to Dermatophagoides pteronyssinus and nocturnal wheeze. An electrostatic precipitator was used during the night to remove airborne particles from the bedroom. During use of the precipitator peak expiratory flow rates were no better than in a control period.
A child with cystic fibrosis was given cimetidine in addition to pancreatic extract. Although the stool frequency was reduced the cimetidine had to be withdrawn because meconium ileus equivalent developed.
Zinc levels were measured in serum and hair of normal children and children with cystic fibrosis (CF). The only significant difference found was a higher mean zinc level in hair of CF patients with growth retardation compared to that of CF patients with normal growth.
Faecal samples were taken from three diet-managed phenylketonuric children to determine effects of beta-2-thienylalanine (beta-2-t) on indigenous bacteria. From sample swabs, 127 anaerobes were identified and tested for beta-2-t inhibition on a phenylalanine (Phe)-free medium, Anaerobe Inhibition Test (AIT) agar. Of the isolates, 77.9% grew sufficiently to assay reactions on at least 25% of AIT plates. Using Phe-containing Columbia agar, 86.5% of the strains could be assayed. None of 28 Bacteroides cultures was inhibited by beta-2-t on AIT. Of the genera, Bifidobacterium, Eubacterium, Lactobacillus, Peptostreptococcus, and Propionibacterium, no isolates which would grow on AIT were inhibited. At least one isolate of each of the genera Peptococcus, Fusobacterium, and Clostridium was inhibited. Of 127 total isolates, only nine were inhibited by beta-2-t on AIT, and inhibition was abolished on Columbia agar. Thirty-nine "aerobes" were isolated from the same patients. Strains of the genera tested reacted similarly to previously tested strains from non-PKU sources. Also, anaerobically isolated Excherichia coli were inhibited, while Streptococcus faecalis cultures were not, confirming results on aerobically-isolated non-PKU cultures of the same species. These studies, the first dealing with beta-2-t and anaerobic bacteria, suggest that little change in intestinal bacterial populations might be expected during in vivo beta-2-t treatment.
The possibility of an inborn error of linoleic acid metabolism or of linoleic acid content in cystic fibrosis (CF) was investigated using fibroblasts from children with CF and from control children. Three experiments were done in which fibroblasts were cultured with 1-14C linoleic acid in media containing: (experiment 1) regular fetal calf serum (FCS); (experiment 2) linoleic acid-supplemented FCS; and (experiment 3) delipidated FCS supplemented with linoleic acid. Radioactivity from 1-14C linoleic acid incorporated into the total lipids was quantitatively similar in CF fibroblasts compared to controls in all three experiments. In the first two experiments the radioactivity incorporated into the phospholipid fraction was slightly higher in CF fibroblasts than in controls, whereas radioactivity incorporated into the neutral lipid fraction of CF fibroblasts was slightly lower than in controls. These differences were not found in experiment 3. No differences in linoleic and arachidonic acid composition were found between CF and control fibroblasts in any of the three experiments. The inability to find major alterations in linoleic acid metabolism or content in fibroblasts from children with CF makes a primary metabolic defect in linoleic acid metabolism unlikely.
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Growth comparisons were made, using Shigella, Escherichia, and Salmonella cultures, in liquid and agar-solidified defined media containing beta-2-thienylalanine (beta-2-t). The comparisons were performed to determine the nature of growth inhibition by beta-2-t under different physical growth conditions. In a plate assay, with increasing beta-2-t mixed into the agar, inhibition of Escherichia and Shigella increased. However, Salmonella cultures were not inhibited even at the highest beta-2-t concentrations used. With beta-2-t added to liquid cultures, however, dose-response growth relationships were exhibited by all three genera. The differences occurring in beta-2-t inhibition between liquid and plate assay conditions were not due to composition of culture plates, time of challenge of cultures with beta-2-t, availability of oxygen and associated differences in ratios of volume of media to available surface area, selection of mutants in the plate assay, or to extractable substances from the agar. However, when beta-2-t diffusion into the liquid medium was delayed by using agar plug diffusion cultures, a physiological mechanism was demonstrable which largely protected Salmonella cultures, but not Escherichia and Shigella cultures, from growth inhibition.
Inaccuracies in a commonly used bacterial inhibition assay for blood phenylalanine levels arise when the Mg++ ion concentration in the assay medium is increased. This has practical implications in the diagnosis and management of phenylketonuria.
Serum-immunoreactive-trypsin (I.R.T.) was measured in children with cystic fibrosis (C.F.) and a variety of controls. In the first few months of life all C.F. children had a raised serum-I.R.T. A dried blood-spot assay for I.R.T. was established and has potential as a screening test for C.F. in the newborn.
Mice fed beta-2-thienylalanine (beta-2-T) by oesophageal tube were no more susceptible to gastrointestinal tract colonization by Salmonella typhimurium or Shigella flexneri III than control mice fed water. In both beta-2-T-fed and water-fed groups, the increasing dosage of S. typhimurium, in logarithmic increments to groups of mice, resulted in increasing numbers of these bacteria detectable on dilution plates from organ homogenates. Colonization by S. flexneri III only occurred at a dosage of 10(8) bacteria for both groups. Pretreatment with 50 mg streptomycin allowed 10(3) Salmonella or 10(4) Shigella to colonize both beta-2-T and water-fed groups. Coliforms, inhibited by beta-2-T under certain conditions in vitro, were found in equal numbers in both groups. No obvious differences were noted in either types of other bacteria detected or numbers recovered from the two groups. No gross behavioural changes were noted in mice fed beta-2-T and not challenged with pathogenic bacteria, and no pathological changes were noted in hepatic or splenic tissues. With increasing Salmonella dosage, collections of polymorphonuclear leucocytes, which were almost focal, and increased numbers of giant cells were noted in splenic red pulp areas, in both groups.
Ten children with CF in matched pairs were infused with either Intralipid or with 10% glucose on a double blind basis every other week for one year. Although statistically there was significantly greater gain in height and weight in the study year compared to the previous year only for the test group, both groups improved more than expected. Cumulative data analysis showed greater improvement for the Intralipid group (23 of a possible 45 points) compared to the glucose group (-2 points; P less than .02). This study indicates the need to better define the role of nutrition in the pathophysiology of CF. Meanwhile, it is recommended that all children with CF have plasma linoleic acid levels measured at least once yearly, and if levels are low, appropriate supplements should be given.
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The health of 69 children on Great Barrier Island was studied. This is an isolated community without a permanent doctor, and most children were healthy. Ear disease was the commonest problem, especially in Maori children. Problems of impetigo, scabies, rheumatic fever and dental caries were not present. Comparisons are made with the results of a recent Auckland study.
Human milk was pasteurised at 62.5 degrees C for 30 minutes. This treatment resulted in a 99.99 percent drop in the bacterial count of the milk. Only non-pathogenic organisms remained, and both Escherichia coli and Staphylococcus aureus were destroyed. There was some reduction (less than 50 percent) of the activities of specific antibody to E. coli and lactoferrin, but lysozyme was stable and the pasteurised milk remained effective at inhibiting in vitro growth of E. coli.