Search PubMed⌕ Search

Biomedical subjects

H Sarles

Publications and source records attributed to H Sarles.

At least 55 records · Page 3Linked to original sources

Pancreatic cysts and pseudocysts associated with acute and chronic pancreatitis.

We reviewed 106 consecutive patients with cysts or pseudocysts of the pancreas associated with pancreatitis. A pancreatic fluid collection (PFC) was defined as a limited collection containing pancreatic juice either pure or with pus or blood. Seventy-seven patients presented with chronic pancreatitis (CP) and 29 patients presented with acute pancreatitis (AP). CP-associated PFC was observed in young alcoholic men (mean age 40.8 years) on a high fat, protein, and carbohydrate diet. None of this group had gallstones. In this population, PFC was located in the head of the pancreas in 68% of the cases, was partly extrapancreatic in 22% of the cases, and resolved spontaneously in 9%. AP-associated PFC was as frequent in nonalcoholic men as in nonalcoholic women and presented with gallstones in 48%. They developed later (mean age 53.0 years), resolved spontaneously in 20%, and were located in the body or tail of the gland in 69%. CP-PFC may be designated retention cysts or retention pseudocysts (extrapancreatic); AP-PFC may be designated necrotic pseudocysts.

Acute Disease↗

Occluded pancreatic endoprostheses--analysis of the clogging material.

One of the most common late complications of transpapillary pancreatic endoprostheses is clogging of the endoprosthesis lumen. In this study we analysed the morphology and the biochemical nature of the contents of 10 clogged pancreatic endoprostheses. At the optical level the sludge presented as an organic matrix with embedded small quantities of CaCO3 crystals (and in one case CaCO3 microcalculi). Electron microscopy showed the presence of bacterial ghosts and protein threads. The characteristic pattern of proteolysed pancreatic proteins was obtained when the organic matrix was analysed by SDS-Page. The presence of trypsinogen, amylase and one of the molecular secretory forms of Pancreatic Stone Protein (PSP) was confirmed by Western-blotting. PSP was also found in association with CaCO3 crystals by immunolocalization. These results suggest that endoprosthesis clogging is due to the precipitation of whole pancreatic juice protein, probably triggered by uncontrolled proenzyme activation.

Amylases↗

Pancreatic exocrine responses to secretin, 2-deoxyglucose, a meal, and ethanol after coeliac ganglionectomy in the conscious dog.

The effects of coeliac ganglionectomy on pancreatic exocrine responses to graded doses of secretin, intravenous 2-deoxyglucose 100 mg/kg, ethanol 0.56 g/kg, and 1 g/kg, and to a meat meal were studied in conscious dogs (weight 11 to 27 kg). Five animals underwent coeliac ganglionectomy and up to seven control animals were studied. Coeliac ganglionectomy increased four-fold the pancreatic fluid response to secretin. The early part of the fluid response to 2-deoxyglucose was reduced, but there was no effect on the protein response to 2-deoxyglucose. In controls, ethanol 0.56 g/kg stimulated pancreatic secretion, to nearly double the basal level, but after coeliac ganglionectomy this dose of ethanol inhibited secretion to one third of basal values. There was no effect of coeliac ganglionectomy on pancreatic response to ethanol 1 g/kg. After coeliac ganglionectomy the early response to a meal was increased by 100% for fluid output and by 50% for protein secretion, but from 10 minutes to two hours after the meal there was no effect on pancreatic response. These data shed further light on the mode of action of ethanol on pancreatic secretion, and they indicate that therapeutic coeliac ganglia ablation in man is unlikely to be detrimental to physiological pancreatic secretion.

Animals↗

Pathogenesis and epidemiology of chronic pancreatitis.

Acute pancreatitis is not the cause but may be a complication of chronic pancreatitis. Different forms of chronic pancreatitis are described. The most frequent type in all climates, chronic calcifying pancreatitis, has different causes but similar pathological changes. It is a lithiasis in which a new family of molecules. PSP, a calcium stabilizer, plays a dominant role. Studies of chronic pancreatitis have now reached the stage of molecular biochemistry.

Alcoholism↗

Secretory pancreatic stone protein messenger RNA. Nucleotide sequence and expression in chronic calcifying pancreatitis.

The pancreatic stone protein and its secretory form (PSP-S) are inhibitors of CaCO3 crystal growth, possibly involved in the stabilization of pancreatic juice. We have established the structure of PSP-S mRNA and monitored its expression in chronic calcifying pancreatitis (CCP). A cDNA encoding pre-PSP-S has been cloned from a human pancreatic cDNA library. Its nucleotide sequence revealed that it comprised all but the 5' end of PSP-S mRNA, which was obtained by sequencing the first exon of the PSP-S gene. The complete mRNA sequence is 775 nucleotides long, including 5'- and 3'- noncoding regions of 80 and 197 nucleotides, respectively, attached to a poly(A) tail of approximately 125 nucleotides. It encodes a preprotein of 166 amino acids, including a prepeptide of 22 amino acids. No overall sequence homology was found between PSP-S and other pancreatic proteins. Some homology with several serine proteases was observed in the COOH-terminal region, however. The mRNA levels of PSP-S, trypsinogen, chymotrypsinogen, and colipase in CCP and control pancreas were compared. PSP-S mRNA was three times lower in CCP than in control, whereas the others were not altered. It was concluded that PSP-S gene expression is specifically reduced in CCP patients.

Adolescent↗

Pancreatic stone protein: quantification in pancreatic juice by enzyme-linked immunosorbent assay and comparison with other methods.

To quantitate pancreatic stone protein (PSP), a competitive radioimmunoassay using monoclonal antibodies to PSP extracted from pancreatic stones and a sandwich enzyme-linked immunosorbent assay (ELISA) using monospecific polyclonal antibodies to the secretory forms of PSP (PSP S) were established. When PSP concentrations were measured in pancreatic juice by radioimmunoassay, no difference could be found between patients suffering from chronic calcifying pancreatitis and other diagnostic groups. Yet, with the ELISA technique involving polyclonal antibodies, decreased concentrations were found in chronic calcifying pancreatitis patients when compared to controls (p less than 0.001), chronic alcoholics without pancreatic symptoms, or obstructive pancreatitis patients. These discrepancies are discussed. The monoclonal antibodies recognizing the C-terminal part of PSS S (PSP S1), results from the radioimmunoassay indicate that the concentration of that polypeptide is identical in the juice of controls and patients. Results from the ELISA obtained with polyclonal antibodies raised against PSP S2-5 molecules, i.e., recognizing the PSP S1 part and the N-terminal portion of the molecule, indicate that the differences observed reflect differences in the juice concentration of that N-terminal peptide.

Antibodies↗

Chronic calcifying pancreatitis: epidemiology and current concept of the lithogenesis.

The exact aetiology of chronic calcifying pancreatitis is unknown; several factors that lead to the development of this well-defined disease have been identified. Epidemiologic studies and careful analysis of nutritional data played an important role in precising the risk represented by alcohol consumption and dietary habits, and characterized the geographical distribution of the disease. At the same time, biochemical modifications of the pancreatic juice were described in alcoholics; later on, a new family of pancreatic secretory protein, the so-called "Pancreatic Stone Protein" was discovered. While its secretory form (PSP S2-5) prevents calcium crystal formation from the supersaturated pancreatic juice, its partially degraded form (PSP S1) is insoluble and probably the main protein of intraductal and intraacinar precipitates. Recent studies have confirmed that in chronic calcifying pancreatitis patients the mRNA encoding the synthesis of PSP S2-5 is decreased, and the protein is diminished both in the zymogen granules and in the pancreatic juice.

Calcinosis↗

Calcium carbonate saturation in human pancreatic juice: possible role of ductal H+ secretion.

Saturation with calcium carbonate was measured in human pancreatic juice anaerobically collected for diagnostic purposes in 15 patients who were ultimately found not to have pancreatic disease. Bicarbonate, PCO2, proteins, and total and ionized calcium were measured in samples collected every minute during a 20-min period after intravenous administration of secretin (1 U/kg) and, 10 min later, caerulein (75 ng/kg). All samples were supersaturated with calcium carbonate. The first sample (washing-out sample) contained the highest concentrations of ionized calcium (Ca2+) and proteins but was least supersaturated with calcium carbonate. Washing-out samples also differed significantly from samples under caerulein by having a lower pH (7.52 +/- 0.30) and higher PCO2 (103.1 +/- 32.20 mmHg) versus 8.22 +/- 0.15 and 38.4 +/- 4.5 mmHg, respectively. Values of PCO2 increased and bicarbonate concentration decreased linearly with protein concentration in washing-out samples but not under hormonal stimulation. This suggests that a concentration of pancreatic juice occurs in pancreatic ducts in association with luminal H+ secretion and CO2 formation, which results from bicarbonate neutralization. During stimulation, ionized calcium concentration increased with protein concentration without any change of PCO2, so that supersaturation was more pronounced under caerulein than under secretin stimulation. Disturbances of the ductal concentration of pancreatic juice during interdigestive periods could be important for pancreatic stone formation in humans.

Bicarbonates↗

The human pancreatic stone protein.

Chronic calcifying pancreatitis (CCP) is characterized by the presence of stones in pancreatic ducts. Calcium carbonate (CaCO3) is the main constituent of stones, to which is associated an organic matrix consisting primarily of one protein of Mr 14,000, the pancreatic stone protein or PSP. PSP is not present as such in pancreatic juice, but in polymorphic forms with higher molecular weights. These secretory forms (PSP S2-5, Mr 16-19,000) are synthesized in the acinar cells of the pancreas and secreted along the same secretory pathway as the exocrine enzymes. The heterogeneity of the forms of higher Mr (PSP S2-5) is probably due to different glycosylation patterns. PSP and PSP S1 are generated by the cleavage of an Arg-Ile bond in the N-terminal part of PSP S2-5. The N-terminal sequence of PSP (40 amino acids) is identical to that of PSP S1, whose complete sequence (133 amino acids) has been determined. Yet, the two proteins differ by their pI. Pancreatic juice is normally supersaturated in CaCO3, suggesting the presence of a stabilizer preventing CaCO3 precipitation. The PSP S could play that role, since an activity inhibiting the nucleation and growth in vitro of CaCO3 crystals was found in pancreatic juice, associated with these proteins. Moreover, PSP S concentration was significantly lower in the pancreatic juice of patients with CCP than in control patients. Proteins homologous to PSP S were also found in the dog, rat, swine, monkey and ox. They constitute a new family of pancreatic secretory proteins, whose biological role would be to maintain pancreatic juice in a stable state towards CaCO3.

Amino Acid Sequence↗

Exocrine pancreatic function and protein-calorie malnutrition in Dakar and Abidjan (West Africa): silent pancreatic insufficiency.

Pancreatic function was measured by duodenal aspiration after injection of secretin and cholecystokinin in malnourished children from Dakar and Abidjan, West Africa, and in age- and sex-matched control subjects from Dakar, Abidjan, and Marseille, France. Compared with French control subjects, pancreatic function was moderately decreased in Abidjan control subjects and more severely in Abidjan subjects with kwashiorkor. Pancreatic insufficiency was as severe in patients as in control subjects in Dakar. After a well-balanced diet was fed for 5 d, all kwashiorkor symptoms disappeared. In Abidjan pancreatic secretion levels increased but remained lower than in control subjects. After 28 d feeding, the pancreatic secretion of kwashiorkor patients in Dakar was not modified. Pancreatic extracts had no effect on changes in pancreatic insufficiency after feeding. In West Africa there is a latent pancreatic insufficiency involving water, electrolytes, and enzymes, which is more severe in Dakar, where, in contrast to Abidjan, it is neither aggravated by kwashiorkor nor corrected by feeding.

Blood Glucose↗

Diet, pancreatic function, and chronic pancreatitis in south India and France.

The usual consumption of calories, fat, protein, and carbohydrate, and the exocrine pancreatic function estimated in duodenal juice after an intravenous injection of secretin and cholecystokinin (CCK), have been studied with the same method and by the same team in Kerala (South India) and in Marseille (France) in apparently normal children (7 Indians, 21 French), in normal adults (23 Indians, 17 French), and in patients presenting with chronic calcifying pancreatitis (8 Indian children, 28 Indian adults, 25 French adults). Although they had a low protein intake (children controls: 32.1 +/- 14 g/day (SM), children pancreatitis: 51.1 +/- 15, adult controls: 51.3 +/- 4.9, adult pancreatitis: 55.7 +/- 5.7), the exocrine secretion of Indian controls was not very much modified in comparison with Europeans. Therefore, Indians are less affected by the insufficient diet than the population of Ivory Coast previously studied by the same group. The diet of Indian patients is characterized by a moderately low protein intake and a very low fat intake (18.5 g/day +/- 2.3 (SM) for children 23.4 g/day + 2.7 for adult patients). Comparison between different series of patients studied in different countries with the same method suggests that kwashiorkor or cassava consumption have no evident role in the etiology of chronic tropical pancreatitis. The possible role of a low fat diet is suggested and needs further exploration.

Adolescent↗

Chronic obstructive pancreatitis due to tiny (0.6 to 8 mm) benign tumors obstructing pancreatic ducts: report of three cases.

Three cases of obstructive pancreatitis are described in nonalcoholic women aged 56 to 58 years with a 2-month to 5-year history of recurrent attacks of pancreatic pain associated with intermittent raised serum pancreatic enzymes. The diagnosis was made by sonography showing an enlarged hyperechogenic tail of the pancreas, with a dilated duct, the rest of the pancreas being normal, and by ERCP showing a partial stenosis of the main pancreatic duct with regular dilatation of collateral branches distally to it. Surgical resection of the pancreatic tail cured all three patients. In the obstructed part of the pancreas, the lesions are typical of obstructive pancreatitis with perilobular and sometimes intralobular fibrosis of the same degree in the different lobules of the diseased area and not patchy as in chronic calcifying pancreatitis. The changes in collateral ducts are not marked, and there is an absence of intraductal plugs. Fat necrosis and pseudocysts may be found. Tumors responsible for the obstruction were the smallest islet cell tumors (0.6 and 8 mm) and serous cystadenoma (5 mm) responsible for symptoms ever published. Cephalad to the stricture, the pancreas was normal. When the etiology of chronic pancreatitis is atypical, especially when it occurs in nonalcoholic women aged greater than 50 years, a careful sonography (or computed tomographic scan) and ERCP must be done. Serial sections of the resected pancreas at the level of the obstruction and distal to it are often necessary to demonstrate the tumor.

Adenoma, Islet Cell↗