Aminopyrine breath test in alcoholic liver disease and in patients on enzyme-inducing drugs.

The 14C-aminopyrine breath test was used to measure liver function in 14 normal subjects, 16 patients with alcoholic cirrhosis, 14 alcoholics without cirrhosis, and 29 patients taking a variety of drugs. The normal value for the breath test was 8.6 +/- 1.5%, whereas it was significantly lower (5.1 +/- 3.8%) in patients with alcoholic cirrhosis. Higher than normal values were found in some alcoholic patients without cirrhosis and in patients receiving enzyme-inducing drugs, such as phenobarbitone. There was a significant correlation between serum gamma-glutamyltransferase and breath test in these groups. Some patients with alcoholic cirrhosis may also be capable of enzyme induction.

An analytical method for the quantitation of mannitol and disaccharides in serum: a potentially useful technique in measuring small intestinal permeability in vivo.

An electrochemical-HPLC method for the determination of mannitol and lactulose is presented which may facilitate routine testing of intestinal permeability by requiring only a single blood sample instead of a 6-hour urine collection. Chromatographic conditions are described which allow separation of the closely related sugars lactulose and the dietary disaccharides lactose and sucrose. Preliminary results in normal controls and patients with untreated coeliac disease are presented.

Small intestinal lactase status, frequency distribution of enzyme activity and milk intake in a multi-ethnic population.

The aims of the study were to investigate the prevalence of primary lactase deficiency, frequency distribution of lactase activity and the relationship between lactose intake and lactase activity in three ethnic groups resident in Birmingham. Seventy-two white, 103 Indian and 58 Afro-Caribbean adult dyspeptic patients had distal duodenal biopsies taken for disaccharidase assay at endoscopy. Ten percent of whites, 51% Indians and 81% Afro-Caribbeans had primary lactase deficiency (sucrase/lactase ratio > 4). There was a generalized unexplained depression of disaccharidase activities in the Indians. Frequency distribution of lactase activity for the whole population showed a negative skew without evidence of trimodality. Lactose intake and symptoms attributed to lactose were assessed in a subgroup of 20 whites, 20 Indians and 18 Afro-Caribbeans by questionnaire. Lactose intake did not differ between lactase persistent and deficient subjects both within each racial group and between the groups. Diarrhoea, bloating and cramps were not significantly more common in lactase deficient than lactase persistent individuals.

Reaction rate retardation as a method for serum alkaline phosphatase isoenzyme measurement.

A method for serum alkaline phosphatase isoenzymes using an enzyme reaction rate analyser is described. The complete urea-induced degradation of enzyme activity is monitored, from which individual isoenzyme activities are obtained by calculating the constituent exponential components of the degradation curve. Activities have been measured with adequate sensitivity and selectivity for up to four isoenzyme components in normal and in pathological sera. The identity of each isoenzyme present is assigned from its characteristic degradation half-life, and by this method bone and liver alkaline phosphatase are clearly distinguished and quantitated, and a composite value for placental-intestinal alkaline phosphatase activity is obtained. The approach promises to be applicable to a wide range of isoenzymes, and in analogy with 'reaction rate' the term 'reaction rate retardation' is suggested for the procedure.

The nature of the copper complexes in bile and their relationship to the absorption and excretion of copper in normal subjects and in Wilson's disease.

Copper in bile has been shown by electrophoresis to occur neither as free ions nor complexed to protein but to be associated with a component of the micellar complexes of bile. Solvent fractionation studies suggest that the bile salt components of the lecithin-bile salt complexes are the active binding agents. The effects of specific bile salts on the behaviour of copper during electrophoresis supports this possibility. The relationship of certain bile salts to the excretion of copper in man during the time that an external biliary fistula was functioning and to the intestinal absorption of copper in the rat was found to confirm this concept. The results show that copper in bile is associated with taurochenodeoxycholate and suggest an explanation for the elevated tissue copper levels found in Wilson's disease.

Serum immunoglobulin and protein concentrations in Zambian African patients in Lusaka.

Serum immunoglobulins IgG, IgA, IgM and IgD and gamma-globulin, total globulin and albumin concentrations have been determined in 136 adult Zambian African hospital in-patients, with several diagnoses, in Lusaka, Zambia. The study gives base-line data for that population. A significant positive correlation between serum IgG and gamma-globulin concentrations (P less than 0.001) suggests that for routine use the less costly method for serum gamma-globulin determination gives equally useful information as that for IgG.

Predicting outcome of paracetamol poisoning by use 14C-aminopyrine breath test.

The 14C-aminopyrine (14C-amidopyrine) breath test, carried out within 24-36 hours of an overdosage of paracetamol, was used to predict the extent of liver damage in 30 seriously poisoned patients. Mean 14CO2 excretion was 4.4% in 20 healthy control subjects; 5.5% in six patients who escaped injury; and 2.9%, 1.5%, and 0.2% in those with mild to moderate (12 patients), severe (eight patients), and fatal (four patients) liver damage respectively. This test proved to be a more reliable predictor of the extent of liver damage than plasma paracetamol concentration or half life or the results of conventional liver function tests and may enable treatment of hepatic failure to be started at an early stage.

Measurement of human fetal blood flow.

Real-time B-mode ultrasonography was combined with a pulsed Doppler ultrasound technique for transcutaneous measurement of human fetal blood flow in the aorta and intra-abdominal part of the umbilical vein. The target vessel was located and its diameter measured in the two-dimensional real-time image. The pulsed Doppler transducer was attached to the real-time transducer at a fixed angle. By processing the Doppler shift signals the instrument estimated the mean and maximum blood velocities and the integral under the velocity curves. This permitted calculation of the blood flow. The method was applied to 26 fetuses in normal late pregnancies. Mean blood flow in the descending part of the fetal aorta based on maximum velocity was 191 ml/kg/min. Mean flow in the intra-abdominal part of the umbilical vein was 110 ml/kg/min. This method of measurement is non-invasive and opens new perspectives in studying fetal haemodynamics.

Diffusion of polyethylene glycol-400 across lipid barriers in vitro.

1. Polyethylene glycol has been used extensively as a probe to measure passive small-intestinal permeability in vivo. However, there has been some uncertainty as to its suitability for use as an indicator of the permeation of water-soluble molecules across the intestinal wall because it seems to traverse the mucosa in much greater quantities than sugar molecules of equivalent M(r). 2. We have measured the permeation of polyethylene glycol-400 and lactulose from aqueous solution across pure lipid solvents in vitro. We found considerable transport of polyethylene glycol-400 across chloroform (1.03 g h-1 m-2) but no movement across petroleum ether. 3. However, in a separate experiment in which phospholipid (egg lecithin) was dissolved in the petroleum ether, permeation of polyethylene glycol-400 did occur (0.13 g h-1 m2), implying interaction of polyethylene glycol-400 with the phospholipid. No permeation of lactulose was seen in any of the experiments. 4. Our results suggest that, because of its interaction with lipid solvents, polyethylene glycol-400 is unsuitable as a probe to measure passive intestinal permeability in vivo.

Sucrosemia in untreated celiac disease: a potential screening test.

During studies to develop serum tests of small intestinal permeability, we detected an unidentified disaccharide in HPLC traces of sera from untreated celiacs. This present study aimed to identify the disaccharide and determine whether the presence of the disaccharide in the serum after an oral challenge had potential as a simple screening test for celiac disease. The disaccharide was identified as sucrose by incubation studies of sera with disaccharidases. Twenty untreated celiacs, 15 treated celiacs, and 20 normal or dyspeptic controls were studied for the presence of sucrose in their serum after an oral load (8 g). The results in celiacs were compared with the presence of serum IgA endomysial antibodies. The 10 normal controls were also given a larger sucrose challenge (50 g). Ten of the untreated celiacs and 10 controls had their brush border disaccharidase activities measured. Sucrose eluted in the same position as the unidentified disaccharide in the HPLC trace and the latter could be removed by incubation with sucrase. All untreated celiacs but none of the treated celiacs had sucrose in their serum after the 8-g oral challenge. None of the controls had sucrose in their serum after the 8-g or 50-g challenges. Three untreated celiacs were IgA endomysial antibody negative as were all the treated cases. Brush border sucrase activity was low in untreated celiac disease. The presence of sucrose in the serum after an oral load shows promise as a noninvasive test for celiac disease.

Phytase activity in the human and rat small intestine.

Phytate is the major storage form of phosphorus in seeds and so is a common dietary constituent. Excessive ingestion of undegraded phytates can cause mineral deficiencies in humans. In addition, phytic acid is antineoplastic in animal models of both colon and breast carcinoma. There have been no previous studies quantifying phytase activity in the human small intestine although it is present in animals. Small intestinal phytase and alkaline phosphatase activity and distribution was measured in vitro in mucosal homogenates from two human small intestinal specimens obtained from transplant donors. Rat intestine was also studied for comparison. Phytase activity was found in human small intestine at low values (30 times less than that in rat tissue and 1000-fold lower than alkaline phosphatase in the same tissue). The activity was greatest in the duodenum and lowest in the ileum. In conclusion, the normal human small intestine has very limited ability to digest undegraded phytates. Although this may have adverse nutritional consequences with respect to metabolic cation imbalances, the presence of undigested phytate in the colon may protect against the development of colonic carcinoma.

Early diagnosis of alcoholic cirrhosis by the aminopyrine breath test.

The aminopyrine breath test was assessed as an indicator of liver damage in a consecutive series of 49 chronic alcoholics admitted for detoxification. Mean 14CO2 excretion for those with compensated cirrhosis was 1.6%, compared with 6.8% for those with histologically normal livers, 4.3% for those with fatty change, and 4.0% for those with fatty change and fibrosis. All patients with cirrhosis had a value below the lower limit of normal (3.2%), whereas only 6 of the other patients had a subnormal value. Repeat studies after 7-10 days' abstinence showed that 14CO2 excretion increased in patients with compensated cirrhosis. In view of the poor prognosis of alcoholic cirrhosis once decompensation occurs, early identification of those at risk is important. The aminopyrine breath test was found to be a conventient and sensitive method for detecting early cirrhosis and lends itself as a screening procedure in the management of alcoholic patients.

Measurement of small intestinal permeability markers, lactulose, and mannitol in serum: results in celiac disease.

To date, tests of small intestinal passive permeability have involved the ingestion of test molecules whose permeation is assessed indirectly by measuring their urinary recovery. Excretion ratios of marker molecules (eg, lactulose-to-mannitol excretion ratio, LMER) are useful clinically. Measurement of permeability markers in serum would improve the convenience of the tests. Our aim was to assess small intestinal permeability in celiac patients using serum lactulose and mannitol levels with calculation of lactulose to mannitol serum ratios (LMSR) and to compare the results with the standard methods using urinary recoveries. Twenty-four newly diagnosed celiacs and 10 control subjects were studied; 10 celiacs were restudied while established on a gluten-free diet. Test subjects and patients ingested 10 g lactulose and 2.5 g mannitol in 50 ml water. In 10 untreated celiacs and the controls, blood was taken from 0 to 120 min and all urine was collected for 6 hr. The remaining 14 untreated and the 10 treated celiacs had a single serum sample taken 60 min after ingestion of the test solution. At 1 hr after ingestion, the mean mannitol level in normals (0.156 mmol/liter) was significantly higher than in untreated celiacs (0.06 mmol/liter). The 1-hr mean serum lactulose level in normals (0.125 micromol/liter) was significantly lower than in untreated celiacs (0.56 micromol/liter). The median 1-hr LMSR in untreated celiacs was 0.42 compared with 0.039 in normals and 0.08 in treated celiacs. There was a significant correlation between LMSR and LMER. Permeability testing using serum measurements of lactulose and mannitol gave comparable results in celiac patients to the tests using urinary recovery of the permeability markers and may prove to be more convenient, especially in pediatric patients.

Small intestinal permeability to mannitol and lactulose in the three ethnic groups resident in west Birmingham.

BACKGROUND/AIMS: Asymptomatic residents of tropical countries have differences in small intestinal morphology and permeability compared with residents of temperate zones. The aim of this study was to investigate small intestinal permeability and morphology in three ethnic groups resident in Birmingham, UK. METHODS: 28 white patients, 101 Indian (Indian subcontinent), and 49 Afro-Caribbean adult patients with dyspepsia had endoscopic distal duodenal biopsies and a hyperosmolar lactulose/mannitol permeability test. Twenty normal white subjects had the permeability test. RESULTS: Lactulose/mannitol excretion ratios (LMER) were: white subjects 0.022 (median), white patients 0.022, Indians 0.031, Afro-Caribbeans 0.033. Differences between the immigrant groups and the two white groups were significant (p < 0.001); 33% of Indians and 45% of Afro-Caribbeans had LMER outside the range of the white groups. Afro-Caribbeans born in the UK had significantly lower LMER than those born abroad (p < 0.05); a similar trend was seen in Indians. Villous height/mucosal thickness ratios, calculated from small intestinal biopsy specimens, were lower in the immigrant groups and correlated inversely with LMER (r = 0.28; p < 0.05). Time resident in the tropics also correlated inversely with LMER. CONCLUSIONS: There were significant differences in small intestinal permeability and morphology between immigrants resident in a Western country and the native white population. The data suggested that these differences were related to environmental factors.

Effect of water-loading on the performance of polyethylene glycol as a marker of small intestinal permeability.

1. Polyethylene glycol has been used extensively to measure small intestinal permeability in vivo. However, polyethylene glycol seems to traverse the intestinal mucosa in much greater quantities than sugar molecules of equivalent M(r). In addition, the recovery of the lowest M(r) polymers of administered polyethylene glycol has been found to be both low and unreliable. 2. To compare the behaviour of a range of polyethylene glycol polymers with sugar probes in vivo, a combined polyethylene glycol/mannitol/lactulose probe was administered sequentially to healthy individuals in the fasted state and under conditions of water-loading. Timed hourly urine collections were made for 6 h. 3. Mannitol and lactulose recoveries were all within the normal range and were unaffected by co-administration of water. The lactulose/mannitol recovery ratios did not vary significantly over the 6 h collection period. In contrast, the recovery of total polyethylene glycol was significantly greater when subjects were water-loaded. Furthermore, proportionally greater quantities of polyethylene glycol M(r) 370 than M(r) 854 were recovered towards the end of the collection period than at the start. 4. Our results show that, in contrast to lactulose and mannitol, excretion of low-medium M(r) polyethylene glycol polymers is highly dependent on co-administration of water. Furthermore, the differential rate of excretion of the low compared with the high M(r) polyethylene glycol polymers suggests that the volume of distribution of the individual polymers may vary with M(r), and smaller polyethylene glycol molecules may undergo considerable renal tubular reabsorption.