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Biomedical subjects

S Pauwels

Publications and source records attributed to S Pauwels.

At least 73 records · Page 4Linked to original sources

The influence of liver disease on the methylation of arsenite in humans.

The capacity for inorganic arsenic (ASi) methylation in 13 healthy volunteers and in 30 patients with different types of liver disease has been assessed by measuring the amount of unmetabolized ASi, monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA) excreted in urine within 24 h after the IV injection of 7.14 micrograms/kg ASi. Liver disease does not affect the percent of the injected dose excreted within 24 h but has striking and opposite effects on the proportions of MMA and DMA. MMA excretion is highly correlated with the 14C-aminopyrine breath test (r = 0.73; P less than 0.05). The reduction in the proportion of MMA excreted in urine and the increase in that of DMA are similar with regard to sensitivity and specificity for detecting liver impairment. Unlike the 14C-aminopyrine breath test, the inorganic arsenic methylation test offers the advantage of being unaffected by treatment with microsomal enzyme inducers.

Adult↗

N-terminal tryptic fragment of big gastrin. Metabolism and failure to influence gastrin 17-evoked acid secretion in humans.

The metabolism and some biological properties of the N-terminal 1-17 sequence of human big gastrin (G-34) were studied during infusion in 5 human volunteers. Radioimmunoassay of the 1-17 fragment in plasma indicated rapid clearance (t1/2, 2.4 min). In doses of 75-1000 pmol X kg-1 X h-1, 1-17 G-34 did not, however, influence basal acid output or G-17-stimulated acid output. Gel filtration of plasma samples taken during the infusion indicated the presence of the 1-17 fragment of G-34, together with three other immunoreactive species. Two of these correspond to N-terminal G-34 immunoreactive forms previously found in human peripheral circulation. A fourth immunoreactive component that eluted late on Sephadex G50 was identified for the first time. This component also occurred in fasting human plasma, where it was the only detectable form of N-terminal G-34 immunoreactivity; its concentration increased during infusion of 1-17 G-34. The identification of this fragment and its concentrations in human circulation after feeding deserves further study. Because the fragments of 1-17 G-34 do not occur in antral extracts, and are not produced when G-34 or its N-terminal fragments are incubated in plasma in vitro, they are presumed to be generated from the 1-17 sequence by the action of peptidases found on capillary walls. The elucidation of the mechanisms involved is essential for an understanding of the metabolic pathways of gastrin.

Adult↗

High serum levels of secretory IgA in liver disease: possible liver origin of the circulating secretory component.

Patients with liver disease frequently display unexplained elevations of serum secretory IgA (sIgA). The sIgA levels in various liver diseases were compared to various biochemical or clinical parameters. Patients with primary biliary cirrhosis, biliary tract obstruction, or acute hepatitis displayed highest sIgA levels. In chronic parenchymal liver disease sIgA levels correlated strongly with serum alkaline phosphatase (r = 0.79), leucine aminopeptidase (r = 0.83), and direct bilirubin levels (r = 0.63), but not with prothrombin time, aminopyrine breath test, or presence of portacaval shunting. In acute hepatitis sIgA correlated best with serum glutamic oxaloacetic transaminase (r = 0.69) but not with bilirubin; in four patients with fulminant hepatitis, sIgA fell rapidly together with all liver enzymes and prothrombin time; it rose quickly again in one patient when parenchymal regeneration occurred. These results suggest a hepatobiliary origin of the serum sIgA in liver disease. In acute hepatitis the persistence of hepatocytes seems necessary for maintaining high serum sIgA levels, suggesting a possible hepatocyte origin of the secretory component.

Adolescent↗

Breath 14CO2 after intravenous administration of [14C]aminopyrine in liver diseases.

The determination of of 14CO2 in breath after oral administration of [14C]aminopyrine has been proposed as a quantitative liver function test. In order to shorten the procedure and avoid misinterpretations related to variable rates of intestinal absorption, the [14C]aminopyrine breath test (ABT) was performed after intravenous administration of [14C]aminopyrine in 21 controls and 89 patients with biopsy-proven liver disease. The specific activity of the first hour sample corrected for body weight (SA1) was the most discriminant expression of breath data. The SA1 value, expressed as the percentage of the administered dose, was 0.86 +/- 0.1% (mean +/- SD) in controls and significantly less in patients (0.46 +/- 0.31%). Low values were observed in patients with untreated chronic active hepatitis (0.16 +/- 0.13%), alcoholic cirrhosis (0.2 +/ 0.15%0, and untreated postnecrotic cirrhosis (0.47 +/- 0.17%). In contrast, normal values were obtained in chronic persistent hepatitis (0.86 +/- 0.13%) and 58% of noncirrhotic alcoholic liver diseases (0.83 +/- 0.27%). The results of duplicate studies were reproducible and SA1 correlated with other conventional liver function tests, including 45-min BSP retention. Among these, ABT was the most sensitive screening test for the presence of cirrhosis, especially in alcoholic patients, where it allowed a sharp distinction between cirrhotic and noncirrhotic cases. The results obtained in chronic hepatitis suggested that ABT may provide a reliable index of the activity of the disease. In our hands, intravenous ABT, performed over a 1-hr period, was a fast, sensitive, and discriminant liver function test.

Administration, Oral↗

Identification of NH2-terminal fragments of big gastrin in plasma.

Molecular forms of gastrin in human plasma were studied by radioimmunoassay using antisera specific for the NH2-terminus of big gastrin (gastrin 34). A plasma enzyme system that destroys immunoreactivity of NH2-terminal fragments of gastrin 34, but not of gastrin 34 itself, has been demonstrated and shown to be inhibited by phenanthroline. Endogenous immunoreactive human plasma gastrin that had been concentrated by immunoaffinity adsorption and separated by gel filtration was shown to consist of gastrin 34, together with peptides corresponding to its NH2-terminal tryptic peptide and a shorter NH2-terminal fragment. The latter material does not occur in antral extracts and cannot be generated by in vitro incubation of plasma and antral extracts, suggesting that it is produced by passage through a capillary bed of gastrin 34 or its NH2-terminal tryptic peptide or both. The results are of significance in understanding the mechanisms of secretion and metabolism of different forms of gastrin.

Adult↗

Tc-99m-diethyl-IDA imaging: clinical evaluation in jaundiced patients.

Hepatobiliary imaging with Tc-99m-N,alpha-(2,6-diethylacetanilide)-iminodiacetic acid (Tc-diethyl-IDA) was performed in 91 jaundiced patients with documented hepatobiliary damage and serum total bilirubin up to 35 mg/dl. There were 56 patients with obstructive jaundice and 35 with hepatocellular disease. Correct discrimination between hepatocellular and obstructive jaundice was possible with an overall accuracy of 90%. Agreement with the final clinical diagnosis was obtained in 97% of patients with hepatocellular disease, and in 86% of patients with obstructive jaundice. The reliability of the test was inversely related to the serum bilirubin concentration. The incidence of true-positive scans dropped from 93% for bilirubin levels below 10 mg/dl to 83% for bilirubin between 10 and 20 mg/dl. Above 20 mg/dl, the demonstration of a mechanical obstruction was possible in only one out of the four patients with obstructive jaundice. The high predictive values of the test illustrate that Tc-diethyl-IDA imaging constitutes a reliable method to demonstrate an obstructive cause for the jaundice as long as the bilirubin level remains below 20 mg/dl.

Bilirubin↗

Clinical evaluation of Tc-99m-diethyl-IDA in hepatobiliary disorders.

N,alpha(2,6-diethylacetanilide)-iminodiacetic acid is a new Tc-99m-labeled radiopharmaceutical primarily excreted through the biliary tract. Its high concentration in the bile allows the imaging of the biliary tree and the gallbladder. Scintigraphic studies were performed in 20 normal subjects and 42 patients suffering from various hepatobiliary disturbances. In normal subjects, the early liver uptake was followed by the accumulation of the tracer in the intrahepatic bile ducts and the gallbladder before its discharge into the duodenum. In cases of hepatocellar damage, the hepatic accumulation of the tracer was clearly depressed. Any acute or subacute disorder of the gallbladder was clearly demonstrated by Tc-99m-diethyl-IDA. In cases of asymptomatic cholelithiasis, we observed delayed visualization of the gallbladder associated with its decreased accumulation of the tracer. The intrahepatic bile ducts were distended in cases of incomplete obstruction of the hepatobiliary ducts, whereas they were never visualized when there was severe hepatocellular damage or complete obstruction of the biliary tree.

Bile Ducts, Intrahepatic↗

Gd-EOB-DTPA enhancement pattern of hepatocellular carcinomas in rats: comparison with Tc-99m-IDA uptake.

The enhancement pattern of chemically induced hepatocellular carcinomas (HCCs) after intravenous administration of the hepatobiliary magnetic resonance (MR) contrast agent gadolinium-EOB-DTPA (ethoxybenzyl-diethylenetriaminepentaacetic acid) was compared with the uptake pattern of technetium-99m-labeled iminodiacetic acid (IDA), a hepatobiliary radioactive tracer. The hepatocyte uptake of both the contrast agent and the scintigraphic agent has been shown to be driven by the organic anion transporter. The tumors enhanced less than the liver after Gd-EOB-DTPA administration, whereas the Tc-99m-IDA uptake of differentiated HCCs exceeded that of the liver at 30 minutes and 3 hours after administration. The enhancement pattern of a differentiated HCC with Gd-EOB-DTPA does not mirror that seen with Tc-99m-IDA.

Animals↗

Ferumoxides and Tc-99m sulfur colloid: comparison of the tumor-to-liver uptake in focal nodular hyperplasia.

The tumor-to-liver uptake of two reticuloendothelial agents, namely ferumoxides and technetium-99m (Tc-99m) sulfur colloid, was compared in focal nodular hyperplasia (FNH). Twelve patients with FNH who had undergone ferumoxides-enhanced MR imaging and planar Tc-99m sulfur colloid scintigraphy within 1 year were included from the study. Fourteen patients with FNH with a diameter larger than 3 cm were selected for the comparison. The tumor-to-liver ferumoxides uptake was calculated and the Tc-99m sulfur colloid uptake was assessed visually. Fermuoxides uptake was observed in all but one patient with FNH (mean tumor-to-liver ratio = .36). The six tumors showing normal (n = 5) or increased (n = 1) radiocolloid uptake when compared to the liver accumulated more ferumoxides than the eight tumors showing decreased radiocolloid uptake (P < .01). However, in some tumors, no direct relation was observed between ferumoxides and Tc-99m sulfur colloid uptake. Our observations suggest that ferumoxides uptake might not exactly mimic Tc-99m sulfur colloid uptake in FNH.

Adult↗

Atriopeptin III degradation by endopeptidase 24.11: the Cys-Phe bond is not the preferential cleavage site.

Incubation of rANP(5-28)--also called atriopeptin III (AP III)--with purified endopeptidase 24.11 led preferentially to the production of Phe-Arg-Tyr, while other products of minor importance were detected. One of these was identified as rANP(5-25) (atriopeptin I) (AP I). This hydrolysis pattern of endopeptidase 24.11 towards AP III differs from the known favored site of cleavage at the Cys7-Phe8 bond of rANP(1-28). Moreover, by comparison with rANP(1-28), the degradation rate of AP III was slower. These data suggest that N-terminal peptide truncation results in conformational and/or charge modifications leading to a different positioning of the peptide in the endopeptidase 24.11 active site. In most hypothalamic nuclei of the rat brain known to contain AP III and endopeptidase 24.11, the preferential Ser25-Phe26 bond hydrolysis, although supposed to be responsible for a reduced degradation rate, might represent an effective enzymatic pathway of catabolism for AP III.

Amino Acid Sequence↗

[Current data and perspectives on positron emission tomography oncology-radiotherapy].

Positron emission tomography (PET) is one of the most promising diagnostic procedures in oncology. Using the glucose analogue fluorodeoxyglucose, PET produces whole-body images and is highly sensitive for tumor diagnosis and staging. We review three particular clinical situations in which PET-FDG has proven not only its diagnostic accuracy, but also its impact on patient management, i.e., the staging of non-small cell lung cancer, diagnosis and staging of colo-rectal cancer and head and neck cancer recurrence. Image registration yields anatomo-metabolic images that could be used as additional information for the determination of radiation fields. Tracer and technical issues remain to be solved before PET can be routinely used for that purpose.

Bronchial Neoplasms↗

Impaired gastric emptying in diabetic patients with cardiac autonomic neuropathy.

The aim of our study was to measure the gastric emptying rate for a solid meal in diabetic patients who had no gastrointestinal complaints with (group 1, n = 12) or without (group 2, n = 10) cardiac autonomic neuropathy and in normal controls comparable in age and sex (group 3, n = 10). Gastric emptying rate was assessed with a sequential scintiscanning method. The percentages of the initial isotope activity remaining in the stomach at different times (20, 40, 60, 80, 100, and 120 min) after the ingestion of a Tc-99m-labeled test meal and the emptying half-time were calculated. Cardiac autonomic neuropathy was determined by the beat-to-beat variations in heart rate during deep breathing. A significant reduction of the gastric emptying rate was observed in group 1. Indeed, at 80, 100, and 120 min the percentage of residual isotope activity was 73 +/- 4, 60 +/- 6, and 50 +/- 6% (mean +/- SE), respectively, in group 1 versus 61 +/- 3 (P less than .05), 45 +/- 4 (P less than .05), and 32 +/- 4% (P less than .02) in group 2. In group 3, residual isotope activity was 57 +/- 4 (P less than .05 vs. group 1), 41 +/- 4 (P less than .05), and 29 +/- 4% (P less than .02), respectively. Emptying half-time was also longer in group 1 (121 +/- 9 min) than in group 2 (95 +/- 6 min, P less than .05) or group 3 (90 +/- 4 min, P less than .02).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Current advances in the physiopathology of primary motility disorders of the esophagus].

The authors review the recent literature about the classification of primary motor disorders of the oesophagus: achalasia, diffuse oesophageal spasm, nutcracker oesophagus, hypertensive lower oesophageal sphincter and non-specific intermediary disorders. In fact these motility disorders belong to a spectrum of diseases closely related, with chronological transformation of a specific disorder to another one or to intermediary disorders. Most of the recent pathophysiological research concerned primary achalasia, secondary achalasia syndromes being a kind of experimental model. These studies point to a morphological or functional deficiency of postganglionic nerves inhibiting the lower oesophageal sphincter (LOS) through noncholinergic nonadrenergic neurotransmitters. Recent advances in the treatment of achalasia and other motility disorders are not yet based on these findings. Although calcium channel blockers, like nifedipine, lower LOS basal pressure, they are not very useful on long term relief of symptoms of achalasia. Pneumatic dilatations or cardiomyotomy still remain the best methods of treatment of this disease.

Esophageal Achalasia↗

Omeprazole in the treatment of patients with severe reflux oesophagitis not responding to H2-receptor antagonists and ineligible for surgery.

In 42 patients (25 men, 17 women, mean age 62 years) with severe erosive or ulcerative oesophagitis not responding to H2-receptor antagonist treatment over at least 3 months and ineligible for surgery, omeprazole was administered at an initial dose of 40 mg/day, subsequently reduced to 20 mg after healing of the lesions. Patients had monthly clinical, endoscopic, histological and laboratory assessment over the healing period, then were reevaluated 3-monthly over one year, then 6-monthly, during the maintenance treatment. Stages of oesophagitis were based on the Savary-Miller classification, modified for stage I (erosions must be present). With 40 mg omeprazole, healing was observed in 71%, 83% and 90% of the patients after 1, 2 and 3 months of treatment, respectively. After one month of treatment, a complete healing was less frequently observed in patients with stage IV oesophagitis pre-trial (55%) than in the patients with stages I, II and III pre-trial (90%) (p less than 0.05). Ninety per cent of the patients healed at one month were asymptomatic whereas 50% of the patients with incomplete healing still had symptoms, most often dysphagia, rarely heartburn. Maintenance treatment with 20 mg was sufficient in most patients, with a probability of remaining healed of 69% from 9 to 24 months after starting this dosage. In 9 patients with Barrett's oesophagus, the lengths of the circumferential metaplasia were found to be reduced after one year of treatment compared to pre-trial lengths (p less than 0.005). There was no further significant reduction of length after 2 years of treatment. Fasting gastrin was increased in most of the patients, although great inter-patient variability was observed; 50% of the patients had levels not exceeding 5 times the upper limit of normal. There was no consistent increase of enterochromaffin-like cell density in 29 patients investigated up to nearly 2 years of omeprazole administration. The treatment was well tolerated. By inducing a profound and sustained inhibition of acid secretion, as confirmed by pH monitoring, omeprazole promotes healing of the lesions of severe oesophagitis and prevents recurrence of lesions and symptoms. Omeprazole is therefore a valuable treatment for patients ineligible for surgery, particularly in the elderly.

Adolescent↗

[Campylobacter pylori gastritis: review of diagnostic methods].

The presence of Campylobacter pylori in gastric mucosa is a proof of active gastritis. Diagnostic methods are based on endoscopy: culture--histology--cytology--urease test, or on noninvasive tests: C14 urea breath test and serology. The principles, results (sensitivity--specificity), advantages and problems of each test are discussed as well as the choice of a diagnostic method. In practice, we recommend the use of two methods, a morphological one (histology or cytology) and another based on bacterial activity (urease test or culture).

Bacteriological Techniques↗