A prospective, comparative study of the para-aminobenzoic acid test and faecal elastase 1 in the assessment of exocrine pancreatic function.

BACKGROUND: The assessment of exocrine pancreatic insufficiency is part of the routine work-up of patients with persistent diarrhoea or suspected steatorrhoea. Direct and indirect tests for the diagnosis of exocrine pancreatic insufficiency have their drawbacks. Measurement of faecal elastase 1 by enzyme-linked immunoabsorbent assay is a simple, non-invasive, robust test for exocrine pancreatic insufficiency. METHODS: We performed a prospective comparison of the para-aminobenzoic acid test and faecal elastase 1 test in 45 patients being investigated for diarrhoea or suspected steatorrhoea. Details of clinical suspicion, imaging and response to treatment were recorded. RESULTS: Exocrine pancreatic function was normal in 20 patients with normal para-aminobenzoic acid and faecal elastase 1 levels. Eight patients had exocrine pancreatic insufficiency with low para-aminobenzoic acid and faecal elastase 1 levels, which improved with enzyme supplementation. In 14 of the 15 patients with low or borderline low para-aminobenzoic acid and normal faecal elastase 1 levels, a non-pancreatic cause was found; one patient had a false positive para-aminobenzoic acid test. Two had normal para-aminobenzoic acid but low faecal elastase 1 levels. One improved with pancreatic supplementation, and imaging revealed chronic pancreatitis. The other had a false positive faecal elastase 1 test related to profuse diarrhoea. CONCLUSIONS: Faecal elastase 1 estimation is a simple, non-invasive, robust test of exocrine pancreatic insufficiency, performed on an out-patient stool sample. Its diagnostic performance is superior to that of the para-aminobenzoic acid test in investigating patients with diarrhoea or suspected steatorrhoea.

Osteoclast inhibition by pamidronate in metastatic prostate cancer: a preliminary study.

Twenty five hormone manipulated patients with prostate cancer and metastatic bone disease, treated at least 6/12 previously by hormone manipulation, were given intravenous infusions of Disodium Pamidronate (APD) over a 6 month period. Patients received 30 mg weekly for 4 weeks then twice monthly for 5 months. No other treatment was administered during study. Eleven of 17 patients with pain at the start of the study were pain free at the end. Fasting morning calcium excretion and serum osteocalcin fell significantly with Pamidronate (P less than 0.0001) and urine hydroxyproline was lowered in 13/20 evaluable patients at 6 months. Alkaline phosphatase fell in a proportion of patients and five of 17 patients with previously progressive bone scans stabilised (4) or regressed (1) on treatment. Rising acid phosphatase levels were also lowered in five patients. It is concluded that Pamidronate may be effective in palliating bone pain in some patients and has a stabilising influence on abnormally high bone turnover in metastatic prostate cancer. Further controlled studies of the compound are now warranted.

Simple, optimized liquid-chromatographic method for measuring total hydroxyproline in urine evaluated.

We have optimized a method for measuring total hydroxyproline (HYP) in urine by HPLC after release from urinary peptides by solid-phase hydrolysis on Dowex 50W x 8 ion-exchange resin. The HYP was derivatized with 4-chlor-7-nitrobenzo-2-oxa-1,3-diazole, and excess reagent was removed with the use of a 100-mg C18 Bond-Elut cartridge. The HYP derivative was separated isocratically at 30 degrees C on a 250 x 4.6 mm reversed-phase column containing 5-microns particles of Spherisorb S5 ODS-2, with S-carboxymethylcysteine as internal standard. Total assay time was 14 min. The standard curve for the method was linear from the detection limit for HYP, 3.6 mumol/L, to 10 mmol/L. The between-batch CV was less than 5.1% and the mean analytical recovery of HYP was 95% +/- 1.4%. Comparison with a commercially available colorimetric method showed good correlation: y = 1.158x + 19.76 mumol/L (Syx = 74, n = 120), but HPLC results were 15% higher, probably from incomplete hydrolysis with the colorimetric method. This method offers a considerable improvement in assay time, specificity, sensitivity, precision, and cost compared with the colorimetric method.

Reassessment of faecal alpha-1-antitrypsin excretion for use as screening test for intestinal protein loss.

Faecal alpha-1-antitrypsin and 51Cr-albumin losses in 42 patients with either gastrointestinal or hepatic disease were compared. The reference range was derived from measurements in 20 controls without gastrointestinal disease. Alpha-1-antitrypsin excretion was increased in patients with excessive 51Cr-albumin loss, and correlations were found between alpha-1-antitrypsin clearance and 51Cr-albumin excretion. Because of the considerable overlap of faecal alpha-1-antitrypsin excretion between controls and patients, sensitivity and specificity of the test were only 58% and 80%, respectively. This poor reliability could not be explained by sampling error or temporal variations in alpha-1-antitrypsin excretion. These results show that although faecal alpha-1-antitrypsin excretion correlates with 51Cr-albumin excretion when whole groups of patients are studied, its poor sensitivity makes it an unreliable measure of enteric protein loss.

Essential trace element provision to patients receiving home intravenous nutrition in the United Kingdom.

The methods of provision of essential trace elements to patients receiving long-term home intravenous nutrition in the U.K. have been reviewed and their trace element status has been assessed. Over a 2 year period, 57 patients based on 15 hospitals throughout the country were studied. Although biochemical abnormalities of trace element status were frequent, related clinical complications were apparently rare. Zinc provision from commercial preparations generally required further supplementation. Copper requirements were variable. Manganese provision from trace element mixtures and chromium provision from contaminants of other parenteral nutrient solutions were excessive in many cases. Aluminium contamination is not significant in the nutrient solutions currently used in the U.K. The most common depletion state is for selenium which should probably be provided on a routine basis. The clinical consequences of long-term under- or over-provision of trace elements by the intravenous route requires further study.

Comparison of clinical scores and acute phase proteins in the assessment of acute Crohn's disease.

Fifty-two patients with Crohn's disease have been assessed using acute phase proteins and a scoring system. Thirty-nine underwent operation and intra-abdominal abscesses were found in seventeen. Both scores and acute phase proteins have been shown to reflect inflammation due to secondary sepsis in addition to that from active Crohn's disease. The scores were higher, and acute phase changes greater, in patients with sepsis than those without. By choosing a threshold for each variable that excludes patients without sepsis it has been found that a score greater than 181, ESR greater than 45 mm/h, CRP greater than 33 mg/l, orosomucoid greater than 1.8 g/l and albumin less than 26.7 g/l identify sepsis with a specificity greater than 95 per cent and sensitivity greater than 35 per cent. Over 70 per cent of patients with abscesses exceeded one or more of these thresholds. We believe that operative management should be strongly considered if one or more of these criteria are positive as such patients have a greater than 90 per cent chance of having an intra-abdominal abscess. This will prevent these abscesses eroding into adjacent viscera or to the surface with resulting fistula formation.

Intracellular free amino acids in undernourished patients with or without sepsis.

1. Thigh muscle samples for analysis were obtained from 35 control subjects and 12 severely ill patients, of whom five had disease-induced undernutrition and seven had associated sepsis. An improvement in the Bergström technique for analysing muscle needle biopsy samples was used. 2. Muscle water, chloride and DNA were increased in both groups of ill patients, indicating an increase in the extracellular component and loss of muscle protein. 3. Falls in the concentrations of glutamine, glutamate, arginine, histidine, ornithine and lysine and rises in those of glycine, serine, asparagine, tyrosine, valine, leucine, isoleucine, phenylalanine, methionine and tryptophan were observed in the group of ill patients compared with those in the control subjects. The changes were present mainly in the patients with sepsis, significant differences between these and the undernourished ones without associated sepsis being observed in glutamine, lysine, tyrosine, valine, leucine, isoleucine, phenylalanine and methionine. The changes were either absent or slight in plasma. 4. The increased concentrations observed in six essential amino acids in the septic patients, but not in those with undernutrition, is consistent with the increased catabolic rate of sepsis. 5. However, the branched-chain amino acids, and lysine, threonine, arginine, and histidine, were present in lower concentrations than might be expected from catabolism, presumably due to utilization. It is suggested therefore that septic patients might benefit from increased proportions of these amino acids in their feeding regimen.

Tinnitus in a patient with beta-thalassaemia intermedia on long-term treatment with desferrioxamine.

A women with beta-thalassemia intermedia, and iron overload following many years' treatment with oral iron, was treated with subcutaneous desferrioxamine. During the course of this treatment she developed tinnitus, which was considered to be a rare complication of the use of this chelating agent. The mechanism of this effect is not understood.

N tau-Methylhistidine excretion and myofibrillar protein breakdown in patients receiving intravenous or enteral nutrition.

1. N tau-Methylhistidine, nitrogen and creatinine were measured in the urine of 10 volunteers on normal and meat-free diets and in 10 vegetarians, and compared with the results from the urine of eight patients with intestine fistulae on intravenous or enteral nutrition containing no meat. The values obtained were used to calculate fractional breakdown rate of myofibrillar protein. 2. There was a significant fall in the excretion of N tau-methylhistidine and creatinine and in apparent fractional breakdown rates after 2 days on a meat-free diet. 3. One of the patients had lower, and two of the patients had higher, fractional breakdown rates compared with the vegetarians. 4. N tau-Methylhistidine and creatinine excretion may be a useful and non-invasive measurement of myofibrillar protein degradation in patients on meat-free diets. Firm conclusions cannot, however, be drawn without confirmatory, direct measurement of the breakdown rates of muscle protein in vivo.

Response of plasma amino acids to elective surgical trauma.

Venous plasma amino acids have been measured before, during, and after surgical operation in 17 patients. There were no statistically significant changes in plasma amino acid levels during the operation itself, but in the 3 days following operation the concentration of many of the amino acids were altered compared with the preoperative levels. Because some of the changes resemble those seen in early starvation, further studies are necessary to determine whether trauma or starvation is the prime stimulus to the changes observed.

Ntau-methylhistidine in human skeletal and smooth muscle proteins.

1. Fifteen pieces of rectus abdominus muscle and fifteen pieces of taenia muscle were removed from patients undergoing various surgical procedures. 2. The muscles were extracted, hydrolysed and the content of Ntau-methylhistidine was measured. 3. The rectus muscles contained 3.13 +/- 0.7 mumols Ntau-methylhistidine/g fat-free dry solid and the taenia muscles 2.4 +/- 0.6 mumols/g fat-free dry solid. There was a statistically significant difference (P less than 0.05) between these values using the Student's unpaired tau test, although this could have been due to contamination of the taenia muscles with connective tissue. 4. The muscle content of Ntau-methylhistidine was at least 40% higher than the only other reported value and therefore the method of calculating muscle protein breakdown based on Ntau-methylhistidine excretion requires revision.

Assessment of the nutritional state of patients with an intestinal fistula.

The arm muscle area, derived fat-free mass, urinary excretion of 3-methylhistidine and creatinine were measured serially in a group of patients with an intestinal fistula receiving prolonged nutritional support. While the two anthropometric tests appeared reasonable indicators of changes in muscle mass in these patients, the marked intra-individual variability in excretion of 3-methylhistidine and creatinine created problems in interpretation. It is suggested that more use be made of serial anthropometry in district general hospitals as an alternative, simple, measure of nutritional status.

The effect of elective surgery on 3-methylhistidine excretion.

Elective surgical operation in normally nourished patients is associated with an increase of up to 40 per cent in the urinary excretion of 3-methylhistidine during the first three postoperative days. This increase was statistically significant (P less than 0.01) on the second and third postoperative days. This probably represents a minor degree of increased muscle proteolysis, principally due to the operative trauma. The possible effect of postoperative starvation requires further elucidation.

Metabolic problems in the management of a traumatic pancreatic fistula.

A case of persistent, high output, traumatic pancreatic fistula, complicated by the development of a gastric fistula secondary to a pancreatic abscess, is described. The problems associated with the metabolic and nutritional management are discussed.

The identification of a peptide in human parotid saliva particularly active in enhancing the glycolytic activity of the salivary micro-organisms.

A factor in saliva responsible for markedly activating the glycolytic activity of micro-organisms was isolated from parotid secretions and identified as a small basic peptide. Analysis of the peptide showed a high proportion of histidine, lysine and arginine. Its minimum molecular weight was calculated to be between 2500 and 3000.