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Biomedical subjects

H Sarles

Publications and source records attributed to H Sarles.

At least 145 records · Page 8Linked to original sources

[Protein inhibitors of crystallization. Their characterization and potential role in calcium lithiasis].

Human saliva, pancreatic juice and urine are usually supersaturated with respect to calcium phosphate, calcium carbonate and calcium oxalate, respectively. The potential precipitation of these salts is prevented by unusual phosphoproteins which are normally present in these biological fluids. In vitro, such phosphoproteins are able to suppress the crystal growth of calcium salts; their physiological level is high enough to fulfill this function in vivo. The main molecular characteristics of these phosphoproteins are described and their biological function, as crystallization inhibitors, are discussed by the authors.

Calcium↗

[Recurrent acute pancreatitis, associated with pancreas divisum. Clinical study of 12 cases].

Sixty-three cases of pancreas divisum were diagnosed in a series of 2,800 endoscopic retrograde cholangiopancreatographies performed between 1976 and 1982. This anomaly was significantly associated with recurrent pancreatitis. Based on 12 cases in which the only possible causative factor of acute pancreatitis was pancreas divisum, the symptoms of this association are described. There were seven males and five females. Average age at the onset of symptoms was 35.3 +/- 12.4 years. Heavy to moderate consumption of alcohol was never found; protein and fat intakes were within normal ranges. All patients presented with acute recurrent pancreatitis, half of them having suffered three to five attacks. The duration of troubles ranged from 6 months to 14 years. In half of the cases the attacks did not last more than twelve hours and were of moderate intensity. Even in case of frequent attacks, no loss of weight was observed. These features are different from that of chronic calcifying pancreatitis. Ultrasonography showed the intrapancreatic course of the mesenteric vein and/or the appearance of two areas of different tonality in the pancreatic head in 58 p. 100 of cases. Endoscopic retrograde cholangiopancreatography was always able to make the diagnosis of pancreas divisum. After 7 endoscopic and 2 surgical sections of the minor papilla symptoms regressed completely in 4 cases and improved in 3 cases (follow-up 2 to 36 months).

Acute Disease↗

Pancreatic citrate and protein secretion of alcoholic dogs in response to graded doses of caerulein.

Previous studies have shown dissolution of human pancreatic stones in vitro by citrate solution which bind considerable amounts of ionized calcium. Pancreatic citrate secretion has been demonstrated in canine and human pancreatic juices. This study compares pancreatic citrate secretion of chronic alcohol-fed dogs with controls in response to graded doses of caerulein, in order to evaluate possible differences in factors favouring pancreatic lithogenicity. The dose-response-relation of citrate outputs after graded doses of caerulein revealed significantly reduced maximal secretory capacity of citrate in alcoholic dogs. Protein concentrations in juices from alcoholic dogs were reduced for all doses of caerulein but protein outputs were not different. Bicarbonate concentrations and outputs, as well as volumes, were significantly greater in alcoholic dogs. Linear relation were found between citrate and protein secretion. Chronic alcohol consumption in the dog leads to reduced citrate secretion, which is consistent with recent results in humans suffering from chronic calcifying pancreatitis, who secrete significantly less citrate than healthy subjects. The decrease of calcium-chelating citrate could be an additional factor causing increased calcium levels in the pancreatic juice of chronic alcoholics, a circumstance that might favour protein-plug formation and subsequently pancreatic stone formation.

Alcoholism↗

Biphasic action of intravenous ethanol on dog exocrine pancreatic secretion.

The effect of a 20-min intravenous infusion of 1 g/kg of ethanol on a 15% (w/w) solution in isotonic saline on pancreatic secretion was determined in six conscious Beagle dogs provided with Thomas cannulae. Ethanol was given on a background of a prolonged infusion of 0.5 CU/kg/hr of secretin alone or secretin plus either different doses of cerulein (12.5-200 ng/kg/hr), 3 micrograms/kg/hr of pentagastrin, or 200 micrograms/kg/hr bethanechol. Intravenous ethanol had a biphasic action on pancreatic secretion: inhibition during the first 40 min followed by stimulation. When compared to control experiments with intravenous infusion of saline, the inhibition was statistically significant only for volume and bicarbonate output against a background of pentagastrin and for protein output against a background of bethanechol. We propose that alcohol inhibits acetylcholine-mediated protein secretion. The delayed stimulatory effect of ethanol was statistically significant for both ecobolic (protein output) and hydralatic (water and bicarbonate) secretion during infusion of secretin plus 12.5-25 ng/kg/hr cerulein, but not with doses of 50 ng/kg/hr. Although the plateau of secretion before alcohol was roughly similar in the experiments using cerulein and bethanechol, ethanol inhibited protein output and had no effect on bicarbonate output during stimulation with bethanechol. Therefore, the effects of alcohol on pancreatic secretion are influenced by both the type of stimulation and its intensity (dosage).

Animals↗

Simultaneous mechanisms on exocrine pancreatic secretion initiated by alcohol in the conscious dog.

Modifications of pancreatic secretion induced by the infusion of alcohol were investigated in seven Thomas fistula dogs. Acute intravenous injections of low doses of alcohol induced a significant increase of all parameters of pancreatic secretion. On the contrary the acute intravenous injection of high doses of alcohol induced a significant decrease of pancreatic secretion. A prolonged-alcohol intravenous infusion producing a stable blood alcohol level provoked at first a decrease of pancreatic secretion, significant only for protein output, followed by a significant increase of all parameters of pancreatic secretion. A spontaneous return to prealcohol values of pancreatic secretion was observed in all cases even if the blood alcohol level remained high and stable and despite four hours of experimentation. Upon the background of a stable blood alcohol level, pentolinium did not suppress alcohol-induced stimulation of water and bicarbonate outputs but did abolish the postalcohol changes in protein secretion. Furthermore, atropine abolished all postalcohol changes in pancreatic secretion. Consequently, there are two responses (inhibition and stimulation) to alcohol which coexist in normal dogs. They are related to the blood alcohol levels and are transitory. These responses involve the vagus nerves. Alcohol appears to stimulate the exocrine pancreas through receptors at different levels of the nervous system.

Animals↗

Chronic obstructive pancreatitis after healing of a necrotic pseudocyst.

Seven patients presented with chronic pancreatitis localized upstream to a complete stenosis of the main pancreatic duct in its median part. This stenosis seemed to be secondary to the healing of a necrotic pseudocyst after either acute pancreatitis (four patients) or blunt abdominal trauma (three patients). In five patients, after spontaneous regression of the clinical symptoms of the initial pseudocyst, a silent period which ranged from 2 to 5 months was followed by recurrent attacks of pain of lesser intensity and shorter duration (less than 2 days) than observed during the evolution of the initial pseudocyst. These attacks of pain decreased spontaneously with time, probably because of the atrophy of the left part of the pancreas drained by the obstructed duct (in 6 months to 2.5 years). In 2 patients, the initial pseudocyst was revealed at the same time as the obstructive pancreatitis. The histologic features of chronic obstructive pancreatitis have been described. Fibrosis uniformly spread throughout the diseased pancreas with uniform atrophy of the exocrine parenchyma. Dilated ducts showed far less damages than in chronic calcifying pancreatitis. Since spontaneous clinical healing may be observed, surgical treatment is often useless. Only in patients with severe or frequent attacks is a Roux-Y anastomosis with the dilated part of the main pancreatic duct indicated rather than a risky left pancreatectomy.

Adult↗

Diet, alcohol, tobacco and risk of cancer of the pancreas: a case-control study.

In view of the increased incidence of pancreatic cancer and the possible aetiological role of certain dietary factors, a retrospective epidemiological study was undertaken to investigate the roles of tobacco, alcohol, fat, protein and carbohydrate intakes. Sixty-nine patients with pancreatic adenocarcinoma, and 199 normal subjects were interviewed. Data were obtained on life time drinking, smoking and dietary habits. Conditional logistic regression models were used to analyse the relative risk variations. It was shown that the relative risk of cancer of the pancreas increases with fat and alcohol intakes, does not vary with protein intake, and decreases with carbohydrate intake and duration of alcohol consumption. Alcohol may be not directly involved in the aetiology of cancer of the pancreas: its effect could be due to the contents of some alcoholic beverages.

Adenocarcinoma↗

The role of nicotinic receptors in dog pancreatic exocrine secretion.

1 The effects of pentamethonium, an autonomic ganglion blocker, were studied on the exocrine pancreatic secretion of six conscious dogs given intravenous infusions of urecholine, caerulein or pentagastrin on a background of submaximal doses of secretin. 2 Urecholine-induced protein secretion was not affected but both caerulein- and to a smaller extent, pentagastrin-induced protein secretions were depressed by pentamethonium. 3 These results indicate that intravenous caerulein and pentagastrin, but not urecholine, act at least partially via nicotinic receptors. 4 Volume and bicarbonate output were depressed by pentamethonium when stimulated by intravenous caerulein with a background of secretin, but not when stimulated by pentagastrin on a background of secretin. 5 From these data it is suggested that caerulein and pentagastrin may potentiate secretin-stimulated hydrelatic secretion by different mechanisms.

Animals↗

Cholinergic stimulation and inhibition of pancreatic secretion in alcohol-adapted dogs.

There is indirect evidence of increased release of acetylcholine in the exocrine pancreas of chronically alcoholic dogs. Our aim was to ascertain whether altered pancreatic responsiveness to cholinergic stimulation was an associated phenomenon. Pancreatic dose-response tests with graded bethanechol stimulation on constant secretion stimulation, without or with a low dose of background atropine, were performed in four chronic gastric and duodenal fistula dogs after 3 and 12 months of intragastric feeding with ethanol. The secretory protein response was dose-dependently increased by bethanechol in the control dogs but not in the test dogs, after 3 or 12 months of daily alcohol. They responded significantly only to a dose four to eight times greater than the minimum effective dose in the control dogs. Atropine depressed the entire dose-response curve of these dogs but only the response to the greatest doses in the alcohol-treated dogs. In previous experiments caerulein and/or secretin evoked increased secretory responses of bicarbonate in chronically alcoholic dogs, but this was not the case in this study with bethanechol, which did not have a stimulating effect on bicarbonate in either test or control dogs. Concomitant atropine, however, unmasked a bicarbonate-stimulating effect of bethanechol in control but not in treated dogs. It is concluded that chronic alcohol-feeding, already after 3 months, leads to a diminished pancreatic responsiveness to cholinergic stimulation and inhibition of protein output, as evidenced by at least a fourfold increase of the minimum effective dose of bethanechol and diminished inhibitory action of atropine.

Adaptation, Physiological↗

Protein content of precipitates present in pancreatic juice of alcoholic subjects and patients with chronic calcifying pancreatitis.

Chronic calcifying pancreatitis is characterized by the formation of intraductal protein plugs or precipitates and calcified stones in ducts. Similar precipitates may be collected by endoscopic retrograde catheterization of the main pancreatic duct. They are present in the pancreatic juice of alcoholic subjects and patients with chronic calcifying pancreatitis. Protein analysis of these precipitates was performed to try to elucidate the mechanism of stone formation. Two protein fraction were separated by extraction of precipitates. One fraction was easily soluble in saline and contained a small amount of most of the proteins of pancreatic juice. The other fraction was soluble in citrate or ethylenediaminetetraacetate and contained a few proteins with close isoelectric points and identical molecular weight (13,500). These proteins showed immunological identity with the "stone protein" isolated from human pancreatic calculi. Our data demonstrate that the major citrate-soluble protein of precipitates in pancreatic juice is identical with "stone protein". They are strongly support the concept that this protein is the organic matrix of pancreatic stones. Different mechanisms are proposed to explain the phenomenon of protein precipitation that frequently occurs in alcoholic subjects and patients with chronic calcifying pancreatitis.

Alcoholism↗

Repeated I. V. injections of calcium salts give rise to increased exocrine pancreatic cell sensitivity to caerulein and urecholine in the dog.

The persisting modifications induced by repeated intravenous infusion of calcium salts were investigated in five dogs with Thomas fistulae. Five control dogs were also tested. In calcium treated dogs the pancreatic secretion stimulated by graded doses of either caerulein or urecholine showed: a) an increase in the sensitivity of acinar cells to caerulein and urecholine and potentiation by caerulein of the water and bicarbonate response to secretin, in contrast to the decreased sensitivity to secretin alone reported previously. b) an inhibition of water and bicarbonate secretion with urecholine stimulation, c) an inhibition of calcium secretion which was significant with caerulein. These findings could explain the data previously observed on basal pancreatic secretion of calcium treated dogs such as protein hypersecretion with protein precipitates and reduced bicarbonate secretion which are similar to modifications observed in chronic alcoholic dogs and men. These results have a clinical relevance to the understanding of the pathology of chronic pancreatitis.

Animals↗

[Prospective study of the clinical signs, diet, and radiologic changes of the small intestine and the colon in 106 patients with functional intestinal disorders].

A prospective statistical study of clinical symptoms, radiological modifications of the colon and small bowel as judged by a morphometric method and dietary habits was performed in 106 patients who presented with functional intestinal disorders. Four different associations of symptoms and signs were found: a) pain, sometimes heavy, in the left upper quadrant and the ombilical region was associated with morphometric modifications of the small bowel: increased diameter of the upper part, decreased diameter and increased number of folds in the lower part of ileum; b) slight pain of the two upper quadrants and the two flanks was associated with flatulence, and was not correlated with modifications of the radiological aspect of the small bowel and colon; c) constipation and diarrhea were not correlated with any type of morphometric modifications of the colon; d) constipation was significantly correlated with low fiber diet.

Colon↗

[Pseudomyxoma peritonei: a case with multiple metastases. Ultrastructural study and chemical analysis of the mucoid substance].

A patient with spreading pseudomyxoma peritonei probably caused by a tumor of the appendix showing suggestive clinical features is presented. The long evolution was marked by the discovery of gelatinous substance in the stools and in the lumen of the gut, and the appearance of distant metastasis in the lungs, adrenal glands and lymph nodes. Histochemical studies showed that periodic Shiff acid and Alcian blue were fixed by the mucoid substance. The use of toluidin blue (pH 1) revealed metachromosia. Electron microscopy ascertained the presence of enterocytes and mucous cells and revealed a more obvious nuclear disorganisation than by histological microscopy. Biochemical study showed that the mucoid substance extracted from the pseudomyxoma was rich in carbohydrates and could be identified as a mucin on the basis of the composition of its monosaccarides and of the alkali-lability of its glycanprotein linkages. The mucin was weakly hydrolysed by trypsin in vitro but was deeply attacked by the same enzyme after desialylation. These results: a) confirm the possibility of observing spreading distant metastasis in the pseudomyxoma peritonei; b) underline the potential interest of electron microscopic study in case of wavering diagnosis; c) show that the mucoid substance belongs to the group of neutral sulfomucins; d) legitimate, in the future, a trial of palliative treatment by neuraminidase in such cases.

Humans↗