An improved gas chromatographic method for the detection and quantitation of mercaptans in blood.
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Biomedical subjects
Publications and source records attributed to C O Record.
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Six patients with liver damage following paracetamol overdose, one patient with viral hepatitis and six control subjects were infused with sodium L(+) lactate. In controls the results were analysed using a single compartment model while in paracetamol patients a two compartment system was used to derive the fractional rate removal constant and lactate distribution volume. Forearm arterio-venous differences of lactate were also determined in order to assess the role of voluntary muscle in removal of a lactate load. In paracetamol patients with fractional rate removal constant was decreased to less than half the control value (P less than 0.001) while total distribution volume was similar to the two groups. Fasting lactate concentrations were significantly increased in paracetamol patients due to diminished lactate removal since the endogenous production rate of lactate was not significantly different from controls. A greater proportion of the lactate load was removed in voluntary muscle in paracetamol patients (39%) than controls (17%). Since the balance of lactate removal occurs principally in the liver, the decrease in the fractional rate removal constant in patients following paracetamol overdose indicates a severe derangement of hepatic lactate metabolism with a compensatory increase in lactate metabolism in voluntary muscle.
In an attempt to find the extent to which Clostridium difficile could be implicated as the cause of antibiotic-associated diarrhoea, the stools of 53 patients who had diarrhoea after a course of antibiotics were investigated for the presence of C. difficile toxin. Ten of the patients (19%) were found to be positive, but the stools of four out of 53 patients without diarrhoea after a course of antibiotics were also found to contain C. difficile toxin (7.5%). The titre of toxin in patients both with and without diarrhoea fell within the same range (up to 10(-5)). Neither the organism nor its toxin was found in the stool of 26 patients with ulcerative colitis, eight with Crohn's disease, 49 with non-specific diarrhoea, and 27 normal controls. We conclude that, while C. difficile is responsible for a proportion of cases of antibiotic-associated diarrhoea, the concentration of toxin is not the sole factor affecting the severity of this disorder.
The production of antitoxin after Clostridium difficile-induced diarrhoea has not been reported previously. The stool of a patient with prolonged antibiotic-associated diarrhoea contained C. difficile toxin, and the serum neutralised the cytopathic effect of C. difficile toxin in tissue culture.
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The effect of the topical corticosteroid clobetasone butyrate on enzyme activity and morphology of duodenal mucosa was studied in 9 patients with coeliac disease and 10 controls using organ culture techniques. There was significant increase in mucosal alkaline phosphatase, lactase and maltase activities, but inclusion of a soluble extract of gluten reduced this effect. When clobetasone butyrate was also included in the culture medium significant elevations in enzymes were again observed. Enterocyte height was not affected by incorporation of gluten into the medium. Intra-epithelial lymphocyte counts fell significantly during the culture period. This improvement was also inhibited by gluten and overcome by addition of steroid.
10 patients with sub-total villous atrophy were given the topical corticosteroids betamethasone valerate or clobetasone butyrate for a period of 4 months whilst continuing on a normal diet. 5 patients improved symptomatically while red cell folate, urinary xylose and faecal fat excretion also improved. Brush border enzymes increased in patients treated with higher dosages of each drug. Enterocyte height increased and intra-epithelial lymphocytes were significantly decreased although overall morphological appearances remained indistinguishable from untreated coeliac disease. Suppression of the pituitary adrenal axis occurred in 8 patients and there did not appear to be useful separation of topical from systemic activity. These compounds offer no advantage over prednisolone in non-responsive coeliac disease.
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During perfusion of an isotonic solution containing 56 mmol/l glucose and 122 mmol/l sodium chloride, net movements of water and sodium and glucose absorption were measured in the absence and presence of intraluminal hydrocortisone along 20-cm segments of proximal jejunum in five normal subjects and five patients with active coeliac disease. In normal subjects, the mean net absorption of water and sodium was significantly increased in the presence of hydrocortisone decreased. In the coeliac patients, the mean net secretion of water and sodium was significantly decreased. In neither group was the effect of hydrocortisone associated with a significant increase in glucose absorption. Similar changes in net movements of water and sodium occurred in both groups, even though absorption of hydrocortisone in coeliac patients was 44% of the control value. These results suggest that hydrocortisone may have exerted a local effect on the mucosal transport of water and sodium.
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1. Oral glucose-tolerance tests (100 g) were carried out in six patients with stable well-compensated cryptogenic cirrhosis and in 12 control subjects. 2. In confirmation of previous studies, patients with cirrhosis had high post-glucose serum insulin levels and were glucose intolerant (mean incremental glucose area 954 +/- 186 compared with 482 +/- 35 mmol 3 h-1 l-1 in controls; P < 0.05). 3. Forearm arteriovenous differences of glucose and forearm blood flow were measured to estimate the proportion of the glucose load metabolized in peripheral tissues. Values in cirrhotic patients and control subjects (5614 +/- 1630 compared with 5344 +/- 672 mumol of glucose min-1 l-1 of forearm in 3 h) were similar despite higher glucose levels and sustained high insulin levels in the cirrhotic patients. 4. Peak lactate concentrations after glucose were of similar magnitude in the two groups (0.66 +/- 0.12 compared with 0.62 +/- 0.75 mmol/l) but in the patients with cirrhosis the peak occurred later and was more sustained. 5. The glucose intolerance of cirrhosis is primarily due to impaired hepatic retention of the glucose load. Insulin resistance in peripheral tissues may also be important since the higher insulin concentrations found in cirrhotic patients failed to enhance peripheral glucose uptake.
The pharmacokinetic disposition of prednisolone was studied following oral administration (10 mg) to eight patients with untreated coeliac disease of mild or moderate severity, seven coeliac patients on a strict gluten-free diet and ten normal subjects. No significant differences were shown in the peak prednisolone level, the time of the peak level, the area under the concentration versus time plot, the plasma half-life and the 24 h urinary recovery of prednisolone in the three subject groups. There was however considerable variability within each group. It is concluded that the presence of coeliac disease does not significantly alter the absorption or elimination of prednisolone.
Lactate elimination was studied in twenty-six healthy volunteers during primed constant lactate infusion or multiple lactate injection tests, at blood lactate concentrations of 1-8 mmol-1. Although lactate elimination fitted a single exponential curve over a 30 min period, a significant correlation between the rate removal constant (KL) and the peak blood lactate concentration (Lphi) was demonstrated: loge KL = -2.43-0.132 Lphi (P = 0.003, r = 0.63, n = 20) This suggests that lactate removal does not follow first order kinetics over a wide concentration range but becomes saturated at relatively low blood lactate concentrations. Estimates of the lactate distribution volume did not differ significantly at different dosage levels, but remained in the range 270-300 ml kg-1. Skeletal muscle uptake accounted for about 26% of the infused lactate load. Seven patients with well-compensated hepatic cirrhosis were compared with a group of six control subjects during primed constant infusion tests. Fasting and steady state blood lactate concentrations achieved were similar in both groups. A significant prolongation in lactate half-life was demonstrated in the cirrhotics (18.8 +/- 1.4 min (mean +/- SEM) compared to 14.7 +/- 2.2 min; P less than 0.02). Since peripheral uptake of lactate in the forearm was similar in the two groups, this suggests that hepatic lactate uptake was impaired, due either to hepatocyte dysfunction or portal diversion.
Three dialysis membranes, including a polyacrilonitrile membrane, a polycarbonate membrane and a cuprophan membrane coated with charcoal, have been compared with cuprophan in order to assess their ability to clear from aqueous solution and plasma, substances thought to be of pathogenetic importance in hepatic coma (ammonia, short chain fatty acids and mercaptans), some protein bound (glycocholate and bromsulphthalein) and some middle molecular weight molecules (ethylenediaminetetracetic acid, cyanocobalamin and inulin). High clearance of ammonia, short chain fatty acids and mercaptans were found with membrane tested but dialysis was relatively ineffective for removal of protein bound molecules. Cyanocobalamin, glycocholate and ethanethiol were removed best by the carbon coated membrane and by combining dialysis with adsorption, this membrane may offer advantages over other treatments for liver failure.
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Four cases of ileo-caecal tuberculosis in Asian immigrants were seen in a 6-month period at The London Hospital. Although rare in Caucasians, this condition is an important cause of gastrointestinal symptoms in this ethnic group. Definitive diagnosis can frequently be made only by histological examination and culture of biopsy material obtained at laparotomy. However, in suitable cases, where there is a high index of clinical suspicion, a trial of chemotherapy may be preferable to operation. If laparotomy is performed, resection with subsequent chemotherapy is the treatment of choice.
Clinicians administering potent therapeutic agents must be aware of their side-effects. The gut is an important site of adverse drug reactions and drug-induced disease must always be considered in the differential diagnosis of patients presenting with gastrointestinal symptoms. A careful drug history must therefore be taken in all such patients. Symptoms can often be related to drug ingestion, but late effects also occur. The presence of blood in vomitus or stool is pathognomonic of serious pathology which may be drug-induced and requires further investigation. Upper gastrointestinal haemorrhage and pseudomembranous colitis are potentially fatal manifestations of drug therapy. Gastrointestinal symptoms can often be avoided if therapy is taken with meals or in a smaller dose, but drug withdrawal is always the first line of management in patients whose symptoms may be drug-induced.
Marked pancreatic islet cell hyperplasia was found in a patient with laxative-induced diarrhoea. It is suggested that laxative abuse might be an important aetiological factor in patients with pancreatic islet cell hyperplasia and the watery diarrhoea syndrome but in whom no hormonal excess can be demonstrated.