Growth retardation in asthmatic children treated with inhaled beclomethasone dipropionate.
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Biomedical subjects
Publications and source records attributed to A W Johnson.
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1. The measurement of the intestinal metabolism of the nitrogen moiety of glutamic acid has been investigated by oral ingestion of l-[15N]glutamic acid and sampling of arterialized blood. 2. Measurements have been made in six normal adults weighing an average of 72.8 kg ingesting 100 mg of l-[15N]glutamic acid after an overnight fast. 3. Measurement of the enrichment of arterial glutamic acid, glutamine and alanine was by gas chromatography-mass spectrometry. Isotopic enrichment of the amino acids was followed for 150 min after the ingestion of the amino acid. 4. Arterialized venous blood amino acid concentrations, measured by h.p.l.c., demonstrated no significant changes during the course of the experiment. 5. From the observed appearance of label in arterialized glutamic acid, alanine and glutamine, little luminal glutamic acid reaches the extracellular pool. The majority of the administered nitrogen label appears in the arterial alanine and glutamine components.
Over the past 5 years, the Leeds Regional Cystic Fibrosis (CF) Unit has provided comprehensive annual assessments of CF patients that include dietary assessments and fat absorption studies. Enteric-coated microsphere pancreatic enzyme preparations (microsphere preparations) were compared to conventional enzymes as therapeutic agents for these patients. Presently in the U.K., two microsphere preparations are licensed for use and a further two products are likely to receive licenses in the near future. The success of these preparations is dependent on the ability of the microsphere coating to resist dissolution until the pH exceeds approximately 5.5 and thus prevent inactivation of lipase in the acid environment of the stomach. A study comparing Pancrex V Forte, a conventional enzyme preparation, to three microsphere preparations, Pancrease, Creon, and pancreatin Merck, confirmed the superiority of Pancrease and Creon over Pancrex V Forte and pancreatin Merck with regard to control of symptoms, and nitrogen and fat absorption. Because of differences in the physical characteristics of various microsphere preparations, the dissolution rates of Pancrease, Creon, and pancreatin Merck were compared in vitro. In aqueous buffers, striking differences among the preparations were seen at pH 5.5; whereas only 25% of available lipase was released from Creon, both Pancrease and pancreatin Merck show almost complete dissolution at this pH. Only at pH 6.5 and above do all three preparations show complete dissolution. In duodenal juice, as in aqueous buffers, lipase release from Creon takes place at a lower rate than with the other two preparations until pH 6.0 or higher is attained.(ABSTRACT TRUNCATED AT 250 WORDS)
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Protein metabolism after surgery in the presence of disseminated malignancy has been investigated and compared with results obtained from patients undergoing similar surgical procedures for benign disease and localized malignancy. Whole body nitrogen turnover, measured by primed continuous infusion of 15N glycine, was highest with disseminated malignancy. Similarly rates of whole body protein synthesis and breakdown, calculated from turnover and nitrogen excretion (nitrogen intake being zero), were elevated in the presence of disseminated malignant disease. The increased rates of protein metabolism may represent adaptation to the demands of inevitably growing malignant tissue.
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Twenty-seven patients with infiltrating gastric carcinoma received chemotherapy as the first stage in management to reduce tumour extent and viability in preparation for subsequent surgery. All patients who had received no previous treatment for their cancers were included in the study, regardless of the type or extent of the primary gastric lesion; there was no patient selection. In 25 patients chemotherapy was administered by intra-arterial infusion, while in two patients it was given intravenously. Of 21 patients who underwent repeat gastroscopy before surgery, 11 (52%) showed endoscopic improvement. Gastric resection was carried out in 24 of the 27 patients. The perioperative mortality was 11% (three of 27 patients). Of the 27 patients, 14 were initially assessed as having advanced incurable lesions. Only two of these remain well and apparently free of tumour. The other 13 patients were considered to have resectable and potentially curable lesions at the time of referral. Of these, 11 remain well and apparently free of tumour between one and five years after diagnosis; the other two patients in this group died from postoperative complications.
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Intestinal surgery is usually associated with the parenteral administration of sodium and water, sometimes in amounts considerably in excess of excretory capacity. We have studied the effect of this situation on the water content of the gut at and 5 cm from a single-layer end-to-end anastomosis in the rabbit. Water content was measured by desiccation. One group of animals (group 1) did not receive intravenous therapy. The second group (group 2) received 5 ml kg-1 h-1 of Hartmann's solution during the operative period and thereafter to a total volume of 200 ml by 48 h. In group 1 there was a 5-10 per cent increase in tissue weight both at the anastomotic site and at 5 cm (P less than 0.01, Mann-Whitney U test) on the first 3 days. Thereafter, water content at the anastomosis persisted, but resolved in normal gut. In group 2 a further 5 per cent increase in weight over group 1 occurred (P less than 0.01), persistent at the anastomotic site over 5 days, though resolving elsewhere after 2 days. Extracellular fluid volume expansion exaggerates an anatomical third space present in the region of an anastomosis. At the suture line, oedema so induced is persistent and could be deleterious.
Although urine volume (and, less frequently, concentration) is often measured in the perioperative period, little attempt has been made to separate temporal phases of the intra- and postoperative response to surgery. In 7 patients undergoing standard severe single trauma and managed by a conventional regimen which included intraoperative Hartmann's solution, we have investigated the hourly pattern of urine solute and electrolyte excretion over the first 48 h. Contrary to expectation, in the first 5 h Na+ excretion increases in association with overall solute excretion, and thereafter progressively diminishes. K+ excretion increases 4 h postoperatively and remains elevated for 24 h, after which it returns to normal, even though Na+ excretion remains low. Free water excretion is negative for the first 24 h, though urine osmolality does not suggest a maximal antidiuretic response by the kidney--the highest concentration achieved being just below 800 mosmol/kg. In order to distinguish between the physiological adaptive changes due to starvation and those due to injury, the hourly pattern of urine solute and electrolyte excretion was further investigated in 12 healthy volunteers mimicking postoperative conditions. Apart from the early postoperative period, the hourly pattern of Na+, K+ and osmolar excretion shows no discernible difference from the operated group. These results show that, particularly in relation to Na+, the changes seen in the post-injury patient, even after major uncomplicated surgery, are largely adaptive, and this is especially striking at 24 h after surgery.
Quantitative relationships between skin sensitization potential and certain physico-chemical properties of alkylating agents have been reported. This study demonstrates the correlation of the relative alkylation index (RAI), derived from the alkylation rate and lipophilicity of an alkylating agent, with a set of experimental sensitization data obtained for a series of p-nitrobenzyl compounds.
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Early weight gain by starving patients managed with total parenteral nutrition has been regarded as spurious - that is, merely an increase in body water. We designed an experiment to mimic the starved state in which glycogen stores are depleted and sodium intake is very low. The subjects were then repleted with a sodium-free, high carbohydrate intake. All subjects who received potassium gained weight and switched to a respiratory exchange ratio which suggested mainly carbohydrate oxidation. From changes in weight and total body water the weight gain was calculated to be the consequence of glycogen storage with 1 g of glycogen obligating 3.21 +/- 0.57 g water. Two patients with total dysphagia showed a similar pattern. Two subjects who did not receive potassium showed a rise in respiratory exchange ratio but failed to store glycogen. Early weight gain in patients who received high-carbohydrate feeding after starvation is a normal phenomenon and represents a return to a more hydrated state consequent upon glycogen repletion.
A maximization test (after Magnusson & Kligman 1970), a single injection adjuvant test (SIAT) and a modified Draize test procedure for assessing contact sensitization potential in guinea-pigs have been compared for their ability to detect 19 known human contact sensitizers. The results show that the modified Draize procedure is a good screening test particularly for strong sensitizers. The maximization procedure is a very stringent test of sensitization potential, able to detect some marginal sensitizers. The sensitivity of the SIAT procedure is sufficiently similar to that of the maximization test to act as an alternative for routine testing, particularly in view of its practical advantages over the maximization procedure.
1. A kinetic approach to the determination of the number of functional active sites per molecule of the adenosylcobalamin-dependent enzyme, ethanolamine ammonia-lyase, is described. 2. Time courses for formation and breakdown of a cob(II)alamin intermediate during reaction of the enzyme, fully saturated with adenosylcobalamin, with L-2-aminopropanol as substrate, were followed using a stopped-flow spectrophotometer under two conditions: (a) enzyme concentration much greater than that of substrate, (b) substrate concentration much greater than that of enzyme. 3. Results were analysed in terms of a three-step mechanism involving binding of substrate (k+1 step), cob(II)alamin formation (k+2 step) and cob(II)alamin breakdown (k+3 step). the kinetic scheme was shown to be sufficient to account for the observed time courses and rate constants of 80 s-1 (k+2) and 1.5 s-1 (k+3) were determined. 4. The number of active sites per enzyme molecule (n) was calculated from the kinetic data in three ways: (a) calculation from amplitude of absorbance measurement, (b) calculation from measurements of the values of rate constants and (c) analysis by computation of the kinetic data using the computer program FACSIMILE. A value for n close to 6 was calculated by each of these methods. This value is in disagreement with the literature value of about two sites per molecule but is consistent with the I6II6 subunit structure of the enzyme. 5. Kinetic analysis of data from experiments in which the adenosylcobalamin concentration was varied while substrate and enzyme concentrations remained constant showed that all the active sites function with identical rate constants. 6. The principle and mathematical basis of the kinetic method for determining the value of n is given as an Appendix.