Biomedical subjects
Publications and source records attributed to N B Roberts.
A simple and precise separative procedure can now be used to isolate individual pepsins from gastric juice, and by measurement of the protein absorbance at 280 nm enable their direct quantitation. This will facilitate the study of pepsin secretion, particularly in patients with peptic ulcer disease.
We have shown that pepsin 1 can be prepared in milligram quantities from human gastric juice by semi-preparative high-performance ion-exchange chromatography. Further investigation into the elution of this enzyme using linear chloride gradients have shown it to be a heterogeneous mixture, the components of which all have peptic activity, but differing specific activities. These components are changed in number and retention time by incubation with hyaluronidase and aryl sulphatase, but not by neuraminidase or acid phosphatase, implying the presence of a sulphated proteoglycan.
Total amino acid losses were measured daily in the ultrafiltrate collected from eight patients with acute renal failure treated by continuous high-flux venovenous hemofiltration. All patients had type-1 respiratory failure and required mechanical ventilation. Four patients also suffered cardiogenic shock and were dependent on two or more inotropic drugs; the other four had Escherichia coli septicemia. All patients received identical daily parenteral nutrition as a continuous infusion. The overall mean serum amino acid values were greater in the group with cardiogenic shock (180 +/- 36 [SEM] mumol/L) compared to those with septicemia (131 +/- 26 mumol/L; p less than .05). The daily ultrafiltrate losses of amino acids were also greater, 4.2 +/- 0.7 mmol/24 h (1.1 g N) compared to 2.1 +/- 0.3 mmol/24 h (0.6 g N, p less than .05). For all patients there was a positive correlation between the serum amino acid value and ultrafiltrate loss (r = .84, p less than .001). However, the slopes of the regression curves for the two groups differed (p less than .001), suggesting that for the same plasma value the ultrafiltrate loss was greater for those patients with cardiogenic shock.
Amino acid losses were measured daily in a non-septic patient who was continuously haemofiltered for 7 days at an ultrafiltration rate of 1,000 ml/h and then for a further 7 days at 500 ml/h. During this period she received an infusion of 9 g nitrogen each day. At the higher ultrafiltration rate the mean amino acid loss was 7.9 g/24 h (SEM 0.3 g) and at the lower rate, 2.4 g/24 h (SEM 0.2 g). The losses of amino acids to the ultrafiltrate depended upon the rate of ultrafiltration and upon the free serum amino acid values (r = 0.93, p less than 0.001), but did not depend upon molecular size or charge. The serum amino acid values did not fall during continuous haemofiltration despite loss to the ultrafiltrate, suggesting that the losses were small when compared to the total body pool of free amino acids. However, in septic patients these losses may be of clinical importance in those who are continuously haemofiltered for long periods.
Serum aluminium was monitored in 19 patients admitted with acute oligo-anuric renal failure. The maximum serum aluminium obtained during the course of treatment was greater (p less than 0.05) in 4 patients treated by haemodialysis alone, mean +/- sem 3.78 +/- 0.71 mumol/l than in 4 patients treated only by haemofiltration, 0.60 +/- 0.22 greater (p less than 0.05) during treatment with haemodialysis, 2.7 +/- 0.62 mumol/l than during treatment with haemofiltration, 1.36 +/- 0.15 mumol/l. There was a significant positive correlation between the maximum serum aluminium during treatment with haemodialysis and the number of hours of haemodialysis given (r = 0.76, p less than 0.001). There was no significant increase in serum aluminium due to the administration of human albumin solutions. The aluminium content of dialysate water represents a major source of aluminium in patients with acute renal failure; prevention by reverse-osmosis water purification is recommended.
A serum aluminium assay has been established using a DC plasma emission spectrometer and calibration with serum based standards. The assay is linear between 0.20 and 18.0 mumol/L aluminium. The procedure gives good analytical recovery and precision. The assay was validated by comparison(s) with an electrothermal atomic absorption (ETAAS) procedure which showed good agreement. Serum aluminium concentrations have been compared in normal individuals, in undialysed chronic renal failure patients with or without aluminium hydroxide treatment, and in dialysed patients treated with oral aluminium hydroxide. Non-dialysed patients had higher serum aluminium concentrations if treated with aluminium hydroxide. Haemodialysis patients had the highest serum aluminium concentrations whilst those on peritoneal dialysis had levels similar to those of the non-dialysed chronic renal failure group.
We report six cases of patients with renal failure and exposure to aluminum who developed septicemia. In all cases the serum aluminum increased markedly. This may have contributed to the neurological dysfunction seen in five, and the deaths of four of the patients. We suggest that the rise in serum aluminum was due to the release of tissue-bound aluminum, resulting in an increase in free, diffusable aluminum and that this jeopardized both neurological function and immunocompetence.
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The ability to digest mucus, mucolytic activity of isolated pepsins and samples of human gastric juice has been assayed by measuring the fall in viscosity when incubated with purified pig gastric mucus glycoprotein. Pure human pepsin 1, the peptic ulcer associated pepsin, digested gastric mucus glycoprotein at a faster rate than did pure human pepsin 3 (the principal human pepsin), or the equivalent pig pepsin (pepsin A). At pH 2.0 pepsin 1 had twice the mucolytic activity of pepsin 3. Above pH 3.8 this difference became more marked and whereas pepsin 1 caused substantial mucolysis up to and including pH 5.1, pepsin 3 had minimal activity. At pH 4.0 pepsin 1 had six times the mucolytic activity of pepsin 3. Gastric juices from patients with duodenal ulcer each exhibited substantial mucolytic activity between pH 2 to 5, similar to that of pepsin 1. In contrast, gastric juice from non-symptomatic volunteers exhibited little mucolytic activity above pH 4. Analysis of the mucus glycoprotein by gel filtration showed that an increase in lower molecular weight, pepsin degraded, glycoprotein was associated with the fall in mucus viscosity for all enzyme preparations. These results showed that pepsin 1 can digest the mucus more effectively than pepsin 3 and at higher pH values. The raised concentrations of pepsin 1 in the juice of peptic ulcer patients may thus promote the ulcerative process by increased erosion of the mucus barrier under conditions likely to pertain in the duodenal bulb as well as the stomach.
The effects of somatostatin (SRIF) and its long-acting analogue, SMS 201-995 on the prevention and treatment of acute pancreatitis were studied in rats. Acute pancreatitis was established by ligating the bile duct at the point of entry into the duodenum, thereby allowing reflux of bile into the pancreas. Administration of SRIF (4 micrograms kg-1 body wt IV followed by a 12 h infusion of 4 micrograms kg-1 body wt h-1) or SMS 201-995 (2 micrograms kg-1 body wt SC) at the time of bile duct ligation prevented the increase in the serum concentrations of amylase and lipase observed in control rats 12 h after bile duct ligation. Moreover, SRIF and SMS 201-995 administration prevented development of the histological changes consistent with acute pancreatitis observed in control animals. These results suggest that SRIF or SMS 201-995 may be of value in preventing acute pancreatitis following ERCP or after surgery on the pancreas. In rats with established pancreatitis, SRIF (IV bolus of 4 micrograms kg-1 body wt followed by a 24 h continuous infusion of 4 micrograms kg-1 body wt h-1) or SMS 201-995 (2 micrograms kg-1 body wt SC followed by a similar dose 12 h later): (1) significantly improved survival; (2) produced histological changes in the pancreas consistent with organization and healing; (3) prevented the accumulation of ascitic fluid; (4) reduced the serum levels of amylase and lipase. These results suggest that SRIF and SMS 201-995 may prove valuable in the treatment of established acute pancreatitis in man.
The application of a DC plasma emission spectrometer to the measurement of copper, zinc and magnesium in serum and urine is reported. Each assay requires only a simple dilution in 1% nitric acid. Comparisons with standard atomic absorption techniques showed good analytical agreement, especially for copper and magnesium. Analysis of quality control preparations for copper and zinc gave results ranging from -1.5% to +3.6% of the stated values for five copper and four zinc experiments, with an unexplained result of +7.6% for one zinc experiment. Reference ranges were compiled for serum zinc and urinary copper which agreed closely with those established by atomic absorption and neutron activation analysis. Assays by DC plasma emission are thus precise and reproducible, and simple enough to authenticate the method for use in a clinical laboratory.
Direct-current plasma emission spectrometry determines food calcium and phosphorus, faecal calcium and chromium, and urinary calcium and phosphorus accurately, precisely and rapidly without acid digestion or dry ashing. Food and faeces are homogenised, diluted and aspirated directly into the plasma. The method makes metabolic balances swifter and less labour-intensive; it enables the use of chromium sesquioxide as an inert marker, for perchlorate digestion is avoided. Both plasma emission (-9.9%) and a dry ashing procedure (-13.5%) give lower values for food phosphorus than those derived from food tables.
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Serial measurements of serum amylase, lipase and ionized calcium were made in a prospective study of 17 patients with acute pancreatitis. The mean serum ionized calcium was significantly below the normal range for the first 24 h and had returned to normal after 48 h. There was no correlation between serum ionized calcium and paired calcium corrected for albumin during the first 36 h of the study, but they were correlated for the remainder of the investigation. Serum lipase and ionized calcium levels were just significantly correlated over the first 3 days (r = -0.44; t = 2.3; P less than 0.05; d.f. 22), but failed to reach correlation over the whole period of study (r = -0.34; t = 2.0; d.f. 31). These data establish a significant drop in directly measured ionized calcium early in an attack of pancreatitis, which is not seen in the paired corrected calcium values. Furthermore, the drop is correlated with serum lipase, although this is weak and other factors must be involved in the hypocalcaemia.