Investigation of QT interval in adult coeliac disease.
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Biomedical subjects
Publications and source records attributed to L Gullo.
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Serum concentrations of trypsin and elastase I were determined in 109 HIV Ab-positive patients (52 asymptomatic HIV-infected patients, 25 with lymphadenopathy syndrome, and 32 with acquired immunodeficiency syndrome) to assess the prevalence of possible pancreatic damage in these patients. Serum trypsin was abnormally elevated in 46 of the 109 patients (42.2%): 19 of the 52 asymptomatic HIV-infected patients (36.6%), 9 of the 25 with lymphadenopathy syndrome (36%), and 18 of the 32 with acquired immunodeficiency syndrome (56.3%). Serum elastase 1 was elevated in 14 of the 109 HIV Ab-positive patients (12.8%): 3 of the 52 asymptomatic HIV-infected patients (5.8%), 3 of the 25 with lymphadenopathy syndrome (12%), and 8 of the 32 with acquired immunodeficiency syndrome (25%). None of the patients with abnormally high serum pancreatic enzyme concentrations had clinically evident pancreatic disease. There was no statistically significant difference in serum levels of trypsin and elastase I between drug addicts and nonaddicts, between alcoholics and nonalcoholics, or between those with cytomegalovirus infection and those without. A significant inverse relationship was found between serum enzyme concentrations and the number of CD4+ lymphocytes. The results of this study show that high levels of serum trypsin and elastase are present in an elevated percentage of patients with acquired immunodeficiency syndrome, suggesting that the pancreas is frequently damaged in this disease. The finding of abnormally high serum enzyme concentrations not only in patients with AIDS, but also in asymptomatic carriers and in patients with lymphadenopathy syndrome suggests an association between HIV infection and the development of pancreatic lesions.
A rare case of pancreatic exocrine carcinoma with an endocrine component secreting adrenocorticotropic hormone (ACTH) is reported and discussed in relation to other cases previously published. The patient initially presented with a severe form of diabetes, which was treated accordingly. Persistence of hyperglycemia, along with other metabolic alterations and marked hypokalemia, led to the suggestion of abnormal ACTH secretion. In this patient, however, a florid Cushing's syndrome was not observed. The patient also developed hematological alterations, mainly leukopenia and thrombocytopenia, whose origins were unclear. At autopsy, a poorly-defined mass was discovered between the body and tail of the pancreas. Standard histology showed a moderately-differentiated adenocarcinoma. Immunohistochemical analysis of the tumor specimen demonstrated the presence of some neoplastic cells immunoreactive for chromogranin A, neuron-specific enolase and ACTH. These findings are consistent with the existence of an endocrine component within the exocrine carcinoma with ACTH differentiation.
We studied the effect of a low dose of neurotensin (2.5 pmol/kg/min) on meal- and cerulein-induced gallbladder contraction in 11 healthy volunteers by means of real-time ultrasonography. Ingestion of a meal caused a significant reduction in gallbladder volume which reached a maximum of 57 +/- 2% of the basal value at 60 min after the meal. The infusion of neurotensin caused a slight but not significant attenuation of the contractile response of the gallbladder to the meal (maximal reduction of 49 +/- 6%). Increasing doses of cerulein (10, 20 and 40 ng/kg/h, for 30 min at each dose) caused progressive reductions in gallbladder volume of 18 +/- 5, 72 +/- 5 and 89 +/- 4% with the three respective doses of cerulein used. The simultaneous administration of neurotensin did not significantly modify the gallbladder response to cerulein. The results indicate that neurotensin, at a dose of 2.5 pmol/kg/min, does not influence the gallbladder contraction stimulated by food or cerulein.
Pancreatic pseudocysts are a common and painful complication of chronic pancreatitis. Seven patients (six male, one female; mean age 49.9 years) with chronic pancreatitis complicated by pseudocysts and persistent pain were treated with the pancreatic anti-secretory drug octreotide for 2 weeks. Octreotide caused no notable changes in the size of the pseudocysts of three patients. In the remaining four patients, the pseudocysts decreased in size by a mean of 42% (range 29-52%), and pain disappeared completely. These findings suggest a role for octreotide in the treatment of pancreatic pseudocysts.
The effects of pancreatic polypeptide, thyrotropin-releasing hormone, and glucagon on plasma amino acid uptake by the exocrine pancreas were studied in 12 healthy volunteers aged 22-31 years. Pancreatic amino acid uptake was determined by measuring free plasma amino acid concentration before and during pancreatic stimulation with cerulein (50 ng/kg.h). The administration of this peptide caused a significant decrease (by 14%-20%) in plasma amino acid concentration. Pancreatic polypeptide and thyrotropin-releasing hormone, given at respective doses of 195 pmol/kg.h and 2 micrograms/kg.h, significantly prevented this decrease by 79.3% and 55.8%, respectively. Glucagon, administered at a dose of 7.5 micrograms/kg.h, significantly augmented (by 68.8%) the decreasing effect of cerulein on plasma amino acid concentration. In 2 patients with severe exocrine pancreatic insufficiency, cerulein had no effect on the concentration of plasma amino acids, whereas the addition of glucagon caused a marked decrease. The results indicate that pancreatic polypeptide and thyrotropin-releasing hormone are able to inhibit plasma amino acid uptake by pancreatic acinar cells; this inhibitory effect could be a mechanism by which these peptides decrease pancreatic enzyme secretion. Glucagon does not seem to affect pancreatic amino acid uptake, at least not under the experimental conditions of this study. The decrease in plasma amino acid concentration following glucagon administration was likely the result of the stimulation of amino acid uptake by extrapancreatic tissues by this peptide.
Octreotide (SMS 201-995) is a long-acting somatostatin analogue that inhibits exocrine pancreatic secretion and that has been proposed for treatment of various pancreatic disorders. To gain more information about the mechanism by which octreotide inhibits pancreatic enzyme secretion, we studied the effect of this compound on plasma amino acid uptake by the pancreas in six healthy volunteers aged 22-29 years. Pancreatic amino acid uptake was assessed by measuring plasma amino acid concentration before and during pancreatic enzyme synthesis stimulation with cerulein (50 ng/kg/h). The infusion of cerulein caused a significant decrease (p less than 0.001) in plasma amino acid concentration. The subcutaneous injection of octreotide at dosages of 12.5, 25, and 50 micrograms prevented this decrease in a dose-dependent manner. The decrease in amino acid concentration reached a maximum of 19.4 +/- 2.4% during cerulein infusion and a maximum of 10.7 +/- 2.5, 6.8 +/- 1.2, and 2.9 +/- 1.2% (means +/- SD) when cerulein was preceded by injection of octreotide at 12.5, 25, and 50 mg, respectively. These results indicate that octreotide is able to inhibit the plasma amino acid uptake by pancreatic acinar cells and, consequently, synthesis of pancreatic enzymes. Clinically, this effect could be useful in treatment of pathologic conditions of the pancreas in which it is desirable to suppress acinar cell activity and avoid accumulation of enzymes in acinar cells.
Exocrine pancreatic function was studied in 15 patients with hypothyroidism and 15 healthy subjects by means of the amino acid consumption test, a new tubeless test based on the measurement of plasma amino acid uptake by the pancreas during pancreatic enzyme synthesis stimulation. Nine of the 15 patients were also studied after they had become euthyroid following thyroxine treatment. Pancreatic function was significantly reduced in patients with hypothyroidism compared with healthy subjects. Treatment with thyroxine restored pancreatic function to normal. In two additional hypothyroid patients studied by means of duodenal intubation, pancreatic secretion of both bicarbonate and enzymes was found to be significantly decreased. It was concluded that the thyroid gland plays an essential role in maintaining the functional integrity of the exocrine pancreas in humans.
Octreotide (SMS 201-995) is a long-acting somatostatin analogue that inhibits both basal and secretin-cholecystokinin-stimulated pancreatic secretion. This study assesses the effect of this compound on pancreatic secretion induced by ordinary meals. Three patients with stable secretion of pure pancreatic juice from high output pancreatic fistula were studied. In all three, meal ingestion caused a marked and prolonged increase in pancreatic juice flow, and in bicarbonate and protein output. The subcutaneous injection of 50 micrograms octreotide before meals almost totally prevented (by about 90%) this increase. The inhibitory effect of octreotide on postprandial pancreatic secretion appeared soon, and persisted for the duration of the study period (8 h).
Using fluorescein angiography, we studied the prevalence and characteristics of diabetic retinopathy in 40 patients with chronic pancreatitis complicated by diabetes and in 40 type 1 diabetics with comparable duration of diabetes. Retinopathy was found in 19 pancreatitis patients (47.5%) and in 20 type 1 diabetic patients (50%); it was background, minimal, or mild to moderate, without impairment of visual function, in all 19 pancreatitis patients and in 17 of the 20 type 1 diabetics. In the remaining three idiopathic diabetics, retinopathy was background of severe degree in two and proliferative, with impairment of vision, in one. No differences between patients with and without retinopathy were observed in fasting blood glucose, glycosylated hemoglobin, serum cholesterol, or triglyceride levels. The only significant difference (p less than 0.001) was the greater duration of diabetes in patients with retinopathy when compared with those without it (10.8 +/- 5.7 vs. 5.2 +/- 3.9 yr in pancreatitis patients; 11.2 +/- 5.0 vs. 5.1 +/- 3.5 yr in type 1 diabetics; mean +/- SD). Contrary to what is generally believed, the results indicate that the risk of retinopathy and the characteristics of this complication in patients with chronic pancreatitis and secondary diabetes are similar to those in patients with idiopathic diabetes.
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We measured total plasma amino acid concentrations before and during pancreatic stimulation with secretin (1 clinical unit/kg/h) and caerulein (50 ng/kg/h) in 28 healthy volunteers, 60 patients with chronic pancreatitis (25 mild to moderate, 35 severe), and 22 patients with non-pancreatic digestive disease. In the healthy volunteers and patients with non-pancreatic digestive disease pancreatic stimulation caused a significant decrease (p less than 0.001) in plasma amino acid concentration, whereas in patients with chronic pancreatitis the decrease did not occur or was only slight. In six healthy volunteers and 24 patients with chronic pancreatitis (nine mild to moderate, 15 severe) repetition of the test using caerulein alone showed no significant differences from combined stimulation. Using the maximal per cent decrease in plasma amino acid concentration as an index of pancreatic function (lower normal limit 14%), 20 of the 25 patients with mild to moderate pancreatitis (80%) and 32 of the 35 with severe pancreatitis (91.4%) had values clearly below normal. The overall sensitivity of the test (86.7%) was significantly greater than that of the pancreolauryl test (64.2%) (p less than 0.02) and that of faecal chymotrypsin (66%) (p less than 0.05). None of the patients with non-pancreatic digestive disease had abnormal values. We conclude that the assessment of the decrease in the plasma amino acid concentration during pancreatic stimulation with secretin and caerulein is a simple, sensitive, and highly specific test of pancreatic function. The data obtained using caerulein stimulation alone suggest that the test can be further simplified, and made less costly, by eliminating the use of secretin.
A method has recently been developed for measuring serum pancreatic (P) isoamylase, using two monoclonal antibodies specific for salivary isoamylase. We performed this test on 67 healthy controls and 133 patients: 15 with acute pancreatitis, 53 with chronic pancreatitis (20 during painful relapse and 33 in clinical remission), 18 with pancreatic cancer, 41 with nonpancreatic disease with abdominal pain, five with macroamylasemia, and one with total pancreatectomy. Results were compared with those of a wheat germ inhibition method and with electrophoresis on cellulose acetate. A close correlation was found between the results of immunoinhibition assay and those of the other two tests. All patients with acute pancreatitis had abnormally high values in all three tests. In the group with chronic pancreatitis studied during painful relapse, 16 had an increase in P-isoamylase, as determined with the immunoinhibition assay, 13 with the wheat germ inhibition test, and 15 with electrophoresis. In the group with chronic pancreatitis in clinical remission, we found low values in one patient, by immunoinhibition assay, but found low values in 17 and 19 patients by wheat germ inhibition and electrophoresis, respectively. Low P-isoamylase values corresponded to a severe exocrine pancreatic insufficiency. In the group with pancreatic cancer, the three tests showed similar results, and the majority of the patients had normal values. In the patients with nonpancreatic diseases, abnormally high levels were found in five, by immunoassay, in four by electrophoresis, and in three by the wheat germ inhibition method. In the five cases with macroamylasemia, both inhibition assays erroneously demonstrated an abnormal P-isoamylase elevation. The results show that the three tests are equally useful for the diagnosis of acute pancreatitis, or chronic pancreatitis during an acute relapse. In these diseases, the immunoinhibition test would be the preferred assay because it is simple and rapidly performed.
The effect of cimetropium bromide, a new potent antimuscarinic compound, on caerulein-induced gall bladder emptying in 8 male volunteers was studied by real time ultrasonography. During saline infusion, caerulein (10-40 ng.kg-1.h-1) induced dose-dependent emptying of the gall bladder. There was a significant linear correlation between the dose of the peptide and the reduction in gall bladder size. A continuous infusion of cimetropium bromide (5 mg.h-1) significantly inhibited the contracting effect of caerulein on the human gall bladder, by 74% in response to the lowest dose and by 45% and 22%, respectively, to the two higher doses. The data confirm that the contracting effect of CCK-like peptides on the human gall bladder is at least partly cholinergically mediated, and they demonstrate the relaxing activity of cimetropium previously shown in animals. Provided its antispasmodic activity is also evident in disease, cimetropium should be regarded as a potentially useful agent for the treatment of biliary colic and spasm of the biliary tree.
The serum behavior of amylase, pancreatic isoamylase, lipase, trypsinogen, and elastase 1 was studied in 145 patients with pancreatic disease and in 66 patients with abdominal pain of nonpancreatic origin, for the purpose of evaluating the relative diagnostic utility of their assays. In 34 patients with acute pancreatitis, serum lipase, trypsinogen, and elastase 1 were elevated in all 34, pancreatic isoamylase in 33 (97%) and amylase in 30 (88%). Ten of these acute pancreatitis patients were followed sequentially for seven days: the variations in their serum enzyme levels were parallel, although the lipase, trypsinogen, and particularly the elastase 1 elevations persisted longer than did those of amylase and pancreatic isoamylase. Among the patients with chronic pancreatitis, either in painful relapse (N = 19) or with pancreatic cysts (N = 15), the respective percentages of enzymes elevations were: 79 and 80% for elastase 1, 68 and 67% for trypsinogen, 63 and 73% for pancreatic isoamylase, 58 and 60% for lipase, 53 and 60% for amylase. In the 52 chronic pancreatitis patients studied during clinical remission, serum enzyme behavior varied greatly, and a majority of the assays (60%) were normal; even in the case of severe pancreatic exocrine insufficiency, normal as well as abnormally high and low enzyme values were seen. Highly variable enzyme behavior was also seen in the 40 patients with pancreatic cancer, and elastase I was the most frequently (35%) elevated enzyme in this group as well. Among the patients with abdominal pain of nonpancreatic origin, abnormally high enzyme levels were present in percentages ranging from 6% for lipase to 21% for trypsinogen.(ABSTRACT TRUNCATED AT 250 WORDS)
In the present study we compared sonographic measurements of the main pancreatic duct (MPD) following maximal secretin stimulation (75 CU intravenous in 1 min) in 15 chronic pancreatitis patients (CP) with those of 18 normal control subjects. The mean caliber of the main pancreatic duct was 1.2 +/- 0.4 mm in controls and 1.8 +/- 0.9 in patients with chronic pancreatitis (P less than 0.025). In the control group a dilatation of the duct with a peak at the third minute was found. In patients with chronic pancreatitis a flatter profile of the response curve with a slower increase and inconstant return to basal values was found. A statistically significant difference was found between absolute variations of MPD caliber over basal values (1.7 +/- 1.06 in controls vs 0.8 +/- 0.69 in CP, P less than 0.005) and the dilatation index [(Dmax - D)/D] (1.31 +/- 0.6 in controls vs 0.66 +/- 0.69 in CP, P less than 0.005). The mean percent increase at the third minute was 131% in control subjects vs 53% of patients with CP (P less than 0.0005). In the five cases of CP showing a caliber increase greater than 100%, a persistent dilatation (100-200%) was found 15 min after secretin administration. At this time, the mean percent increase over basal value in controls was 25%.(ABSTRACT TRUNCATED AT 250 WORDS)
We studied the effect of somatostatin on amino acid uptake by pancreatic acinar cells in 12 healthy male volunteers, aged 20-48 yr. Pancreatic amino acid uptake was assessed by measuring free plasma amino acid concentration before and during pancreatic stimulation with secretin (1 CU/kg body wt.h) and cerulein (50 ng/kg body wt.h). Pancreatic stimulation with these peptides caused a significant decrease in plasma amino acid concentrations. Somatostatin, given at the dosages of 0.15 and 1.35 micrograms/kg body wt.h, significantly diminished this decrease. The effect of the higher dose of somatostatin was more marked than that produced by the lower dose, compatible with dose dependence. The results suggest that somatostatin is able to inhibit the amino acid uptake by the pancreatic acinar cells. This inhibitory effect could be an important mechanism by which the peptide decreases pancreatic enzyme secretion.
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