[Cardiac diffusion MRI of recent and chronic myocardial infarction: preliminary results]. / IRM de diffusion cardiaque dans l'infarctus du myocarde récent et chronique: expérience préliminaire.

PURPOSE: To use diffusion weighted MR imaging (DWI), a technique routinely used in patients with stroke, for diagnosis of myocardial infarction (MI). MATERIALS AND METHODS: A breath hold ECG gated DWI sequence (b = 300 sec/mm2) was developped and applied to 7 patients with recent MI (3-15 days), 3 patients with chronic MI (> 6 months) and 4 patients with valvular heart disease without MI (control cases). DWI data were correlated to T2W, first pass perfusion and delayed enhancement data. RESULTS: In all patients with recent MI, DWI showed an area of increased signal with reduction of ADC relative to normal myocardium. Hyperintense lesion on DWI corresponded to areas of delayed enhancement. The diffusion images were normal in patients with chronic MI or no MI. CONCLUSION: Even though no animal model or other reference method is available, these preliminary results indicate that DWI could assist clinicians in detecting recent MI.

Colocalization of centromeric and replicative functions on autonomously replicating sequences isolated from the yeast Yarrowia lipolytica.

Two sequences (ARS18 and ARS68) displaying autonomous replication activity were previously cloned in the yeast Yarrowia lipolytica. The smallest fragment (1-1.3 kb) required for extrachromosomal replication of a plasmid is significantly larger in Y. lipolytica than in Saccharomyces cerevisiae. Neither autonomously replicating sequence (ARS) is homologous with known ARS or centromere (CEN) consensus sequences. They share short regions of sequence similarity with each other. These ARS fragments also contain Y. lipolytica centromeres: (i) integration of marker genes at the ARS loci results in a CEN-linked segregation of the markers, (ii) an ARS on a plasmid largely maintains sister chromatid attachment in meiosis I, and (iii) integration of these sequences at the LEU2 locus leads to chromosome breakage. Deletions performed on ARS18 show that CEN and ARS functions can be physically separated, but both are needed to establish a replicating plasmid.

Secretion of human blood coagulation factor XIIIa by the yeast Yarrowia lipolytica.

The industrial yeast, Yarrowia lipolytica, secretes high yields of an alkaline extracellular protease (AEP), which is synthesized as a preproprotein encoded by the XPR2 gene. We investigated the possibility of using this system for the secretion of human coagulation factor XIII subunit a (FXIIIa). This protein is naturally secreted in the plasma by an unknown, signal peptide-independent mechanism and has so far been found to be nonsecretable in yeast. We have designed six hybrid genes encoding fusion proteins between increasing portions of the AEP preprodomain and the precursor or mature forms of FXIIIa. All constructs directed translocation of the FXIIIa precursor into the endoplasmic reticulum. Transport of the translocated and core-glycosylated hybrid precursor to the Golgi apparatus appeared to be strongly rate limiting, and most of the precursors appeared to be partially proteolysed. One of these constructs directed the extracellular secretion of a low amount of hyperglycosylated FXIIIa. These results indicate that fusion to the yeast AEP signal peptide and dipeptide stretch allows FXIIIa to be translocated, albeit inefficiently, through the endoplasmic reticulum and to follow a classical secretory transit.

Postprandial cholecystokinin secretion in elderly with protein-energy undernutrition.

OBJECTIVE: Malnutrition is currently observed in aged people, and cholecystokinin is an important peripheral satiety signal. The aim of this study was to examine the effect of aging and protein-energy malnutrition on postprandial cholecystokinin (CCK) release. DESIGN: Non-randomized, cross-sectional comparison by age group. SETTING: Gastroenterology section of a teaching hospital. PARTICIPANTS: Twenty-one human volunteers divided into three groups: young healthy subjects (Group 1: mean 29 years, n = 7), aged healthy subjects (Group 2, mean 80 years, n = 7), and aged subjects with an important degree of malnutrition (Group 3, mean 84.6 years, n = 7). INTERVENTION: Each subject ingested a standardized liquid meal after an overnight fast. MAIN OUTCOME MEASURES: Plasma cholecystokinin was measured using a sensitive bioassay before and after the ingestion of the liquid meal. RESULTS: Basal cholecystokinin levels were similar (0.9 to 1 pM equivalent CCK-8) in the three groups. Postprandial levels were significantly increased over basal (P less than 0.05). The maximal cholecystokinin value was lower in Group 1 (3.5 +/- 0.8 pM equivalent CCK-8) and Group 2 (3.3 +/- 0.77 pM equivalent CCK-8) than in Group 3 (8.3 +/- 2 pM equivalent CCK-8) (P less than 0.05). Integrated plasma cholecystokinin was also similar in Group 1 (171 +/- 38 pM.60 min), (P less than 0.05). CONCLUSION: The increase of postprandial maximal levels of cholecystokinin is more related to malnutrition than to aging.

[Incidence, treatment and prognosis of cancer of the pancreas in Haute-Garonne (1982-1986)]. / Incidence, traitement et pronostic du cancer du pancréas en Haute-Garonne (1982-1986).

The characteristics of incident cases of pancreatic carcinoma found in the area of Haute-Garonne (France), as determined by the Digestive Cancer Registry, are reported. Two hundred and forty-six new cases were collected during a 5 year period in a population of 820,000 inhabitants. The annual standardized incidence rate per 100,000 inhabitants was 4.7 for men and 2.6 for women, respectively. This represents a low risk and corresponds to 7 percent of all intestinal tract tumors. The tumors were shown histologically to be adenocarcinoma in 85 percent of cases. The tumor was localized in the head of the gland in 64 percent of cases, while metastases were present at the time of diagnosis in 43 percent of cases. Ultrasonography was the initial investigation (44 percent of cases) and was performed well before endoscopic retrograde wirsungography (12.8 percent) and computed tomography (18 percent). Eighty-six percent of the patients were operated on. Curative surgery, however, was possible in only 12.5 percent of patients. The incidence of carcinoma remained stable during the observation period and no change was noticed with regard to housing conditions. During follow-up, 50 of 215 patients died within one month following the diagnosis (23 percent). Actuarial survival was 36 percent at 6 months, 17.4 percent at one year, and 3.6 percent at 3 years. These data were comparable to those observed in the Côte-d'Or and Calvados areas. These findings suggest that the French Digestive Tumor Registries should develop co-operative studies particularly in the analytic epidemiological fields.

Microscopic examination of bile directly collected during endoscopic cannulation of the papilla. Utility in patients with suspected microlithiasis.

The usefulness of microscopic examination of pure bile directly collected from the biliary tract during endoscopic retrograde cholangiography and without hormonal simulation was prospectively evaluated in 72 patients. According to clinical, biochemical, ultrasonographic, and radiographic data, the patients were separated into two groups: group 1, patients with proven stones (N = 50), and group 2, patients with suspected microlithiasis presenting symptoms suggestive of cholelithiasis but without evidence of macroscopic stones at echography or cholangiography (N = 22). Cholesterol crystals and/or bilirubinate granules were observed (eg, positive examination) in the bile of 41 of the 50 patients of group 1 (82%). Among patients of group 2, seven (32%) had a positive bile examination: cholecystectomy (N = 2) or endoscopic sphincterotomy (N = 5) disclosed minute stones in all cases. In the 15 patients of group 2 with a negative bile examination, cholecystectomy (N = 3), sphincterotomy (N = 2), and clinical (and/or echographic) 20-month follow-up (N = 9) revealed biliary lithiasis in only one patient, in whom recurrent cholangitis led to disclosure of one bile duct stone. According to these results, microscopic examination of bile samples collected during endoscopic retrograde cholangiography exhibited a sensitivity and a specificity for cholelithiasis recognition of 82.7% and 100%, respectively, with a positive predictive value of 88%. We conclude that the accuracy of this method makes it useful to investigate and manage patients with suspected microlithiasis.

[Effects of biliary lithogenesis in acromegalic patients with long-term octreotide (SMS 201-995) treatment]. / Effets sur la lithogenèse biliaire du traitement au long cours par octréotide (SMS 201-995) chez des patients acromégales.

This study was performed to evaluate the risk of gallstone formation during long-term treatment with the long-acting somatostatin analog octreotide (SMS 201-995). Twelve patients (8 men, 4 women--mean age 43 years) treated with continuous subcutaneous octreotide infusion for acromegaly (mean duration 26.5 months, mean dose 541 micrograms/day) were included. Bile collection by duodenal intubation was performed before, during, and 45 days after octreotide treatment in 3, 12, and 8 patients, respectively. Abdominal ultrasonography and/or oral cholecystrography were also performed before (n = 9 patients), during (n = 12), and after treatment (n = 10). Bile examination was normal in the 3 patients controlled before treatment but showed that 58.3 percent of the treated patients had cholesterol monohydrate crystals. After discontinuation of octreotide only 25 percent of patients had cholesterol crystals. In 3 patients (25 percent) treated longer than 6 months, cholesterol crystals occurred prior to the occurrence of small radiolucent gallstones: one patient underwent cholecystectomy because of biliary colic, while in the two others, complete dissolution of stones was obtained after 10 months of treatment with ursodeoxycholic acid given in association with octreotide. None of the 9 other acromegalic patients (including 7 treated more than 20 months) developed stones. Cholesterol gallstone formation seems to be increased in acromegalic patients during long-term octreotide treatment but the exact incidence remains to be determined in larger series of patients.

Amiloride and analogues inhibit Na(+)-H+ exchange and cell proliferation in AR42J pancreatic cell line.

To study the relation between activation of the Na(+)-H+ antiporter and gastrointestinal cell proliferation, we characterized this antiporter in a pancreatic cell line (AR42J) and studied the effects of mitogenic and nonmitogenic agents as well as those of Na(+)-H+ exchange blocking agents on DNA synthesis. Characteristics of amiloride-sensitive Na+ uptake were those of the Na(+)-H+ exchanger: 1) Na+ uptake was increased by intracellular acidification and depended on external [Na+] and pH; 2) concentrations for half-maximal inhibition (IC50) of Na+ uptake (3 mM [Na+] in medium) were 40 nM 5-(N,N-hexamethylene)amiloride (HA) less than 0.1 microM 5-(N-ethyl-N-isopropyl)amiloride (EIPA) less than 1 microM 5-(N,N-dimethyl)-amiloride (DMA) less than 40 microM amiloride; 3) IC50 for amiloride and analogues to inhibit Na+ uptake depended on [Na+] in medium (in 25 mM Na+ medium, the IC50 values were higher than in 3 mM and were 1 microM EIPA less than 10 microM DMA less than 0.3 mM amiloride). Growth factors for AR42J cells (dialyzed fetal calf serum and epidermal growth factor) activated Na+ uptake in a dose-dependent manner. Bombesin, which is nonmitogenic for AR42J cells, also increased Na+ uptake, indicating that activation of the antiporter is not sufficient to initiate cell proliferation in the AR42J cell line. The effects of Na(+)-H+ exchange blocking agents were tested on serum-stimulated cell proliferation. Decreasing external Na+ dramatically decreased AR42J cell proliferation. Amiloride and analogues inhibited [3H]thymidine incorporation in the same range of concentrations as that with which they inhibited Na(+)-H+ exchange.(ABSTRACT TRUNCATED AT 250 WORDS)

Gastric lipase in alcoholic pancreatitis. Comparison of secretive profiles following pentagastrin stimulation in normal adults and patients with pancreatic insufficiency.

The aims of this study were to evaluate the amount of gastric lipase secreted by the stomach in normal adults and to elucidate a possible adaptative secretion of this enzyme in response to pancreatic insufficiency secondary to alcoholic chronic pancreatitis. Forty-one subjects underwent a gastric intubation. Pentagastrin (6 micrograms.kg-1.h-1 IV) significantly increased gastric lipase concentration and output. Stimulated gastric lipase output in seven normal subjects was 12,598 +/- 2036 U/h (by using tributyrin as substrate). Outputs where higher (P less than 0.02) in 17 patients with pancreatic insufficiency who were not drinking alcohol, but were not significantly different in nine patients who continued to drink (20,413 +/- 1778 U/h and 21,953 +/- 4973 U/h, respectively). On the other hand, high gastric lipase outputs were found in eight patients with duodenal ulcers and no evidence of pancreatic dysfunction (23,180 +/- 262 U/h). The time required to reach maximal lipase output (peak output) following pentagastrin stimulation was the same in all groups (approximately 38 minutes) except for the group of patients with pancreatic insufficiency who did not drink alcohol, in whom it was significantly reduced (approximately 26.5 minutes). Secretory patterns of gastric lipase and pepsin were closely comparable. Gastric lipase secretion could be increased in several clinical conditions and particularly in patients with pancreatic insufficiency caused by alcoholic chronic pancreatitis who have been abstinent for a long time.

Protective effect of misoprostol, a synthetic prostaglandin E1 analog, on cerulein-induced acute pancreatitis in rats.

This study was performed to assess the effects of misoprostol, a synthetic prostaglandin E1 analog, on cerulein-induced pancreatitis. Per group of 10 each, male Wistar rats received either cerulein (2.5 micrograms/kg/h subcutaneously), cerulein and misoprostol (500 micrograms/kg intraperitoneally at 0 and 4 h), or saline. Rats were killed 6 h after the first injection. Misoprostol treatment significantly reduced interstitial edema and acinar cell lesions induced by hyperstimulation. Pancreatic amylase and chymotrypsin contents were increased by cerulein and returned towards control levels in the misoprostol-treated group. The lysosomal volume density and the pancreatic beta-D-glucuronidase activity were significantly increased after hyperstimulation. The two parameters were significantly reduced by misoprostol. A protective effect of misoprostol against lesions induced by cerulein hyperstimulation would be a consequence of a lysosomal stabilizating effect.

Na+/H+ exchange in AR4-2J cells: stimulation by growth factors and pancreatic secretagogues.

To study the relationships between activation of the Na+/H+ antiporter and gastrointestinal cell proliferation, we characterized this antiporter in a pancreatic cell line (AR4-2J). In the present study, the effects of mitogenic and non-mitogenic agents and of Na+/H+ exchange blocking agents on DNA synthesis are reported. Dialyzed fetal calf serum (FCS) (0-10%) increased amiloride-sensitive 22Na+ uptake in a concentration-dependent manner. There was a linear relationship between the increase in 22Na uptake and cell number when FCS was added in the 2-10% concentration range. Amiloride and analogs inhibited 3H-thymidine incorporation in the same concentration range as that with which they inhibited the Na+/H+ exchange. IC50 values were 1 microM for 5-(N-ethy-N-isopropyl)-amiloride (EIPA), 10 microM for 5-(N,N-dimethyl)-amiloride (DMA) and 0.1 mM for amiloride, respectively, indicating that activation of the Na+/H+ antiporter is necessary to initiate cell proliferation in AR4-2J cells. Maximal CCK9-induced 22Na uptake was 3.65 times the basal rate and was obtained at 0.1 nM. Maximal 22Na uptake triggered by unsulfated gastrin 17 was 2.51 times the basal rate and was obtained at 0.1 nM. The EC50s of CCK9 and gastrin in stimulating the 22Na uptake were similar at 1 pM. Maximal carbamylcholine-induced stimulation was observed at 0.1 mM and was 2.37 times greater than the basal rate. EC50 was 1 microM. In AR4-2J cells, the activity of the Na+/H+ exchanger seems to be directly involved in the control of cell proliferation. However, stimulation of this exchanger by stimulating factors that are not growth factors suggests that intracytoplasmic alkalinization could regulate other important metabolic processes which, as yet, are unknown.

Effect of long-term intraluminal perfusion of pentagastrin on rat small-intestinal mucosa.

Mucosal changes occurring during long-term intraluminal perfusion of pentagastrin in the duodenum of conscious adult rats (100 micrograms/24 h/kg, 6 days) were studied. Significant increases of labelling and of mitotic indices were noted in the whole small intestine, with an enlargement of the crypt epithelial proliferative compartment. Differential kinetic variations were observed between upper and lower parts of the small intestine when labelling indices were measured in accordance with the cell position in the crypts. Kinetic variations were correlated to the increases of villous and microvillous area. Alkaline phosphatase and leucine-aminopeptidase-specific activities were significantly increased, suggesting modifications of synthesis and/or maturation of these enzymes. The ileal Paneth cell number was also significantly increased in the ileum. Pharmacologic doses of pentagastrin intraluminally perfused have a trophic effect at all levels of the small-intestinal mucosa.

[Comparative efficacy of famotidine and ranitidine in the treatment of acute-phase duodenal ulcer. A French comparative therapeutic trial]. / Efficacité comparée de la famotidine et de la ranitidine dans le traitement de l'ulcère duodénal en poussée. Essai thérapeutique comparatif français.

This multicentric, double-blind and prospective study, which involved 41 French Gastroenterology Units, was designed to evaluate the efficacy and safety of famotidine, 40 mg at bedtime, compared to single dose ranitidine, 300 mg, in promoting the healing of duodenal ulcer. Two hundred and ninety-six patients with endoscopically proven duodenal ulcer were randomly allocated to 2 treatment groups: 148 were treated with famotidine, and 148 with ranitidine. Patients were treated during 4 weeks and then controlled by endoscopy. Unhealed patients at 4 weeks were treated again by the same drug for 2 weeks and then endoscopically controlled. One hundred and nine patients were evaluable in the famotidine group and 111 in the ranitidine group. Groups were well-matched for age, sex, alcohol and smoking habits, and duration of ulcer disease. At 4 weeks of treatment, 86 of the 109 patients treated with famotidine had healed (79 percent) and 74 of the 111 patients treated with ranitidine healed (67 percent). At 6 weeks of treatment, 104 patients had healed in the famotidine group (95 percent) and 101 in the ranitidine group (91 percent). Results were significantly different between the 2 groups at 4 weeks of treatment only (p = 0.039). Among smoking patients, no statistical difference was observed between the 2 groups at 4 and 6 weeks of treatment. By contrast, in non smoking patients, famotidine appeared more effective (83 percent healed) than ranitidine (67 percent) (p = 0.014) at 4 weeks. Both treatments were well tolerated and severe adverse effects were scarcely observed.(ABSTRACT TRUNCATED AT 250 WORDS)

[Functional pancreatic studies in the diagnosis and treatment of chronic pancreatitis]. / L'exploration fonctionnelle pancréatique dans le diagnostic et le traitement de la pancréatite chronique.

The diagnosis of chronic pancreatitis is usually established by clinical history and morphological criteria based on radiological and/or endoscopic (ERCP) findings. When these morphological signs are absent or equivocal, pancreatic function testing is necessary. Direct testing by duodenal intubation with hormonal stimulation is still considered as the reference method ("gold standard"). Numerous indirect tests have been introduced to replace the duodenal intubation which is rarely well accepted and difficult to repeat. Moreover this technique is only available in highly specialized centres. Among the tubeless tests, the Paba test and the pancreolauryl test are gaining interest. Several modifications of these tests have improved their sensitivity and specificity. In most instances, these tests are unable to detect mild pancreatic insufficiency. However their reproducibility in individual cases could be useful for the follow-up of patients with proven pancreatic insufficiency, particularly with regard to the efficacy and the compliance of replacement therapy.